Objective To observe effects of medication use on small airway function,airway inflammation and acute exacerbations in patients with clinically controlled asthma.Methods Forced expiratory flow over the middle half of ...Objective To observe effects of medication use on small airway function,airway inflammation and acute exacerbations in patients with clinically controlled asthma.Methods Forced expiratory flow over the middle half of the forced expiratory curve(FEF25%–75%),percentage of eosinophil,concentrations of eosinophil cationic protein(ECP)and interleukin(IL)-5 in induced sputum were assessed in patients with clinically controlled asthma who were given oral anti-inflammatory agents alone or in combination with inhaled therapy and inhaled therapy alone.Subsequently,acute exacerbations were compared between two groups during the 24-week follow-up period.Results FEF25%–75%in 43 patients with clinically controlled asthma given oral anti-inflammatory agents alone or in combination with inhaled therapy was significantly higher than that in 49 patients given inhaled therapy alone.Meanwhile,the percentage of eosinophils and levels of IL-5 and ECP in patients with clinically controlled asthma given oral anti-inflammatory agents alone or in combination with inhaled therapy were significantly lower than those in patients given inhaled therapy alone.Additionally,the patients with clinically controlled asthma given inhaled therapy were likely to have more acute exacerbation than the patients given oral anti-inflammatory agents alone or in combination with inhaled therapy during the 24-week follow-up period.Conclusion Systemic anti-inflammatory agents may have a greater effect on parameters reflecting small airway patency and reducing acute exacerbations,presumably secondary to reduction in airway inflammation.展开更多
Objective:To observe the effect of vitaminD3 on airway inflammation and osteopontin(OPN)expression on cough variant asthma(CVA)models.Methods:SD rats were randomly divided into blank group,model group and treatment gr...Objective:To observe the effect of vitaminD3 on airway inflammation and osteopontin(OPN)expression on cough variant asthma(CVA)models.Methods:SD rats were randomly divided into blank group,model group and treatment group,each group with 10 rats.The CVA model was induced by intraperitoneal injection combined with aerosolized ovalbumin(OVA),the treatment group was given 100 mg/ml of vitaminD330 minutes before challenge by administered orally.Airway hyperreaction were measured by airway resistance after inhalation of acetylcholine(Ach).Wright-Gimsa staining was used to observe the inflammatory cells in bronchoalveolar lavage fluid(BALF).HE and PAS were used to observe the morphological changes of lung tissue.OPN expression was detected by immunohistochemistry.Results:1)Airway hyperreaction:airway resistance after inhalation Ach in model group and treatment group were significantly higher than that in blank group(P<0.01),airway resistance in treatment group were lower than that in model group(P<0.01);2)Classification of inflammatory cells:The percentage of macrophages,lymphocytes,neutrophils,and eosinophils in the BALF of the model group and the treatment group were increased compared with the blank group(P<0.01),furthermore,the number of treatment group were lower than the model group(P<0.05);3)Morphological changes of lung tissue:a large amount of inflammatory cells and goblet cell proliferation were observed in the lung tissue of the model group,and these changes were slight in treatment group compared with model group;OPN expression in lung tissue:The expression of OPN in model and treatment group were increased compared with blank group(P<0.05),and the treatment group was lower than that of model group(P<0.05).The OPN content was positively correlated with the percentage of inflammatory cells in BALF(P<0.05).Conclusions:Vitamin D3 can reduce airway hyperreaction and airway inflammation in CVA rats.The mechanism may be related to the intervention of OPN expression in lung tissue.展开更多
Objective:To investigate the effect of Fufei Gushen Decoction on airway inflammation and glucocorticoid receptor in rats with chronic obstructive pulmonary disease.Methods:Fifty Wistar male rats were randomly divided ...Objective:To investigate the effect of Fufei Gushen Decoction on airway inflammation and glucocorticoid receptor in rats with chronic obstructive pulmonary disease.Methods:Fifty Wistar male rats were randomly divided into 5 groups:blank control group,COPD model group,Fufei Gushen Yin high,medium and low dose groups,10 rats in each group,except the blank control group,the remaining 4 groups were Smoked combined with lipopolysaccharide(LPS),cold air stimulation to create CODP rat model.After successful modeling,the blank control group and COPD model group were fed with distilled water 3ml/only,Fufei Gushen Yin high,medium and low dose groups were given 1.02,0.51,0.26g Chinese medicine granules/100g/day,respectively.2 times a day for 28 consecutive days.Samples were collected,hematoxylin-eosin(HE)staining was used to observe the pathological changes of lung tissue,and enzyme-linked immunosorbent assay(ELISA)was used to detect the tumor necrosis factor alpha(TNF-α)in the serum and right alveolar lavage fluid(BALF)of rats in each group.),the content of transforming growth factorβ1(TGF-β1),interleukin-17(IL-17A)and matrix metalloproteinase(MMP-9)and tissue inhibitor of metalloproteinase-1(TIMP-1)in the left lung tissue The expression level of real-time fluorescence quantitative polymerase chain reaction(Real-time PCR)rat left lung tissue GRmRNA,immunohistochemistry(IHC)to determine the expression level of left lung tissue glucocorticoid receptor(GR).Results:The content of TNF-α,TGF-β1 and IL-17A in the serum of COPD rats in Fufei Gushen Yin high,medium and low dose groups and BALF were significantly reduced compared with the COPD model group(P<0.05);The expressions of TIMP-1 and MMP-9 in tissues were lower than those in COPD model group(P<0.05);the expressions of GRmRNA and GR in lung tissues were higher than those in COPD model group(P<0.05),and were higher in Fufei Gushen Yin Among the middle-and low-dose groups,the middle-dose group has the most significant effect.Conclusion:Fufei Gushen Decoction can inhibit the release of inflammatory factors in lung tissue of COPD rats,improve airway inflammation and remodeling,and increase hormone sensitivity.展开更多
Background:Mounting evidence,consistent with our previous study,showed thatγ-aminobutyric acid type A receptor(GABAAR)played an indispensable role in airway inflammation and mucus hypersecretion in asthma.Monocyte ch...Background:Mounting evidence,consistent with our previous study,showed thatγ-aminobutyric acid type A receptor(GABAAR)played an indispensable role in airway inflammation and mucus hypersecretion in asthma.Monocyte chemotactic protein-inducing protein 1(MCPIP1)was a key negative regulator of inflammation.Recent studies showed that inflammation was largely suppressed by enhanced MCPIP1 expression in many inflammatory diseases.However,the role and potential mechanism of MCPIP1 in airway inflammation and mucus hypersecretion in asthma were still not well studied.This study was to explore the role of MCPIP1 in asthmatic airway inflammation and mucus hypersecretion in both mice and BEAS-2B cells,and its potential mechanism.Methods:In vivo,mice were sensitized and challenged by ovalbumin(OVA)to induce asthma.Airway inflammation and mucus secretion were analyzed.In vitro,BEAS-2B cells were chosen.Interleukin(IL)-13 was used to stimulate inflammation and mucus hypersecretion in cells.MCPIP1 Lentiviral vector(LA-MCPIP1)and plasmid-MCPIP1 were used to up-regulate MCPIP1 in lung and cells,respectively.MCP-1,thymic stromal lymphopoietin(TSLP),mucin 5AC(MUC5AC),MCPIP1,and GABAARβ2 expressions were measured in both lung and BEAS-2B cells.Immunofluorescence staining was performed to observe the expression of GABAARβ2 in cells.Results:MCPIP1 was up-regulated by LA-MCPIP1(P<0.001)and plasmid-MCPIP1(P<0.001)in lung and cells,respectively.OVA-induced airway inflammation and mucus hypersecretion,OVA-enhanced MCP-1,TSLP,MUC5AC,and GABAARβ2 expressions,and OVA-reduced MCPIP1 were significantly blunted by LA-MCPIP1 in mice(all P<0.001).IL-13-enhanced MCP-1,TSLP,MUC5AC,and GABAARβ2 expressions,and IL-13-reduced MCPIP1 were markedly abrogated by plasmid-MCPIP1 in BEAS-2B cells(all P<0.001).Conclusion:The results of this study suggested that OVA and IL-13-induced airway inflammation and mucus hypersecretion were negatively regulated by MCPIP1 in both lung and BEAS-2B cells,involving GABAAR signaling pathway.展开更多
Allergic asthma,a chronic inflammatory airway disease associated with type 2 cytokines,often originates in early life.Immune responses at an early age exhibit a Th2 cell bias,but the precise mechanisms remain elusive....Allergic asthma,a chronic inflammatory airway disease associated with type 2 cytokines,often originates in early life.Immune responses at an early age exhibit a Th2 cell bias,but the precise mechanisms remain elusive.Plasmacytoid dendritic cells(pDCs),which play a regulatory role in allergic asthma,were shown to be deficient in neonatal mice.We report here that this pDC deficiency renders neonatal mice more susceptible to severe allergic airway inflammation than adult mice in an OVA-induced experimental asthma model.Adoptive transfer of pDCs or administration of IFN-αto neonatal mice prevented the development of allergic inflammation in wild type but not in IFNAR1−/−mice.Similarly,adult mice developed more severe allergic inflammation when pDCs were depleted.The protective effects of pDCs were mediated by the pDC-/IFN-α-mediated negative regulation of the secretion of epithelial cell-derived CCL20,GM-CSF,and IL-33,which in turn impaired the recruitment of cDC2 and ILC2 cells to the airway.In asthmatic patients,the percentage of pDCs and the level of IFN-αwere lower in children than in adults.These results indicate that impairment of pDC-epithelial cell crosstalk in neonates is a susceptibility factor for the development of allergeninduced allergic airway inflammation.展开更多
Exposure to particulate matter 2.5(PM2.5)potentially triggers airway inflammation by activating nuclear factor-κB(NF-κB).Sirtuin 2(SIRT2)is a key modulator in inflammation.However,the function and specific mechanism...Exposure to particulate matter 2.5(PM2.5)potentially triggers airway inflammation by activating nuclear factor-κB(NF-κB).Sirtuin 2(SIRT2)is a key modulator in inflammation.However,the function and specific mechanisms of SIRT2 in PM2.5-induced airway inflammation are largely understudied.Therefore,this work investigated the mechanisms of SIRT2 in regulating the phosphorylation and acetylation of p65 influenced by PM2.5-induced airway inflammation and bronchial hyperresponsiveness.Results revealed that PM2.5 exposure lowered the expression and activity of SIRT2 in bronchial tissues.Subsequently,SIRT2 impairment promoted the phosphorylation and acetylation of p65 and activated the NF-κB signaling pathway.The activation of p65 triggered airway inflammation,increment of mucus secretion by goblet cells,and acceleration of tracheal stenosis.Meanwhile,p65 phosphorylation and acetylation,airway inflammation,and bronchial hyperresponsiveness were deteriorated in SIRT2 knockout mice exposed to PM2.5.Triptolide(a specific p65 inhibitor)reversed p65 activation and ameliorated PM2.5-induced airway inflammation and bronchial hyperresponsiveness.Our findings provide novel insights into the molecular mechanisms underlying the toxicity of PM2.5 exposure.Triptolide inhibition of p65 phosphorylation and acetylation could be an effective therapeutic approach in averting PM2.5-induced airway inflammation and bronchial hyperresponsiveness.展开更多
Interleukin 5(IL-5)plays crucial roles in type 2-high asthma by mediating eosinophil maturation,activation,chemotaxis and survival.Inhibition of IL-5 signaling is considered a strategy for asthma treatment.Here,we ide...Interleukin 5(IL-5)plays crucial roles in type 2-high asthma by mediating eosinophil maturation,activation,chemotaxis and survival.Inhibition of IL-5 signaling is considered a strategy for asthma treatment.Here,we identified MARCH2 and MARCH3 as critical negative regulators of IL-5-triggered signaling.MARCH2 and MARCH3 associate with the IL-5 receptorαchain(IL-5Rα)and mediate its K27-linked polyubiquitination at K379 and K383,respectively,and its subsequent lysosomal degradation.Deficiency of MARCH2 or MARCH3 modestly increases the level of IL-5Rαand enhances IL-5-induced signaling,whereas double knockout of MARCH2/3 has a more dramatic effect.March2/3 double knockout markedly increases the proportions of eosinophils in the bone marrow and peripheral blood in mice.Double knockout of March2/3 aggravates ovalbumin(OVA)-induced eosinophilia and causes increased inflammatory cell infiltration,peribronchial mucus secretion and production of Th2 cytokines.Neutralization of Il-5 attenuates OVA-induced airway inflammation and the enhanced effects of March2/3 double deficiency.These findings suggest that MARCH2 and MARCH3 play redundant roles in targeting IL-5Rαfor degradation and negatively regulating allergic airway inflammation.展开更多
Objective To investigate the effects of 3-methyladenineon airway inflammation,airway hyperresponsivenessand mucus secretion in asthmatic mice,and to explore itsmechanism. Methods C57BL /6J female mice were randomlydiv...Objective To investigate the effects of 3-methyladenineon airway inflammation,airway hyperresponsivenessand mucus secretion in asthmatic mice,and to explore itsmechanism. Methods C57BL /6J female mice were randomlydivided into normal control group ( PBS),OVAgroup(OVA),OVA with 3-methyladenine group (OVA +3-MA),and OVA with 4-phenylbutyrate group (OVA +4-PBA). OVA group,OVA + 3-MA group and OVA + 4-PBA groups were all sensitized and challenged with OVAto establish asthmatic models,while PBS group was givenPBS as a control. At 2 h before challenge,OVA + 3-MAgroup was intraperitoneally injected with 3-methyladenine,and OVA + 4-PBA group was intraperitoneally injectedwith 4-phenylbutyrate. Airway hyperresponsiveness,eosinophils,and pathological changes of pulmonarytissue (hematoxylin-eosin,HE staining) were measuredto confirm the establishment of asthmatic models.展开更多
Background: Airway inflammation is the core pathological process of asthma, with the key inflammatory regulators incompletely defined. Recently, fibroblast growth factor 2(FGF2) has been reported to be an inflammatory...Background: Airway inflammation is the core pathological process of asthma, with the key inflammatory regulators incompletely defined. Recently, fibroblast growth factor 2(FGF2) has been reported to be an inflammatory regulator;however, its role in asthma remains elusive. This study aimed to investigate the immunomodulatory role of FGF2 in asthma.Methods: First, FGF2 expression was characterised in clinical asthma samples and the house dust mite(HDM)-induced mouse chronic asthma model. Second, recombinant mouse FGF2(rm-FGF2) protein was intranasally delivered to determine the effect of FGF2 on airway inflammatory cell infiltration. Third, human airway epithelium-derived A549 cells were stimulated with either HDM or recombinant human interleukin-1β(IL-1β) protein combined with or without recombinant human FGF2. IL-1β-induced IL-6 or IL-8 release levels were determined using enzyme-linked immunosorbent assay, and the involved signalling transduction was explored via Western blotting.Results: Compared with the control groups, the FGF2 protein levels were significantly upregulated in the bronchial epithelium and alveolar areas of clinical asthma samples [(6.70±1.79) vs.(16.32±2.40), P=0.0184;(11.20±2.11) vs.(21.00±3.00), P=0.033, respectively] and HDM-induced asthmatic mouse lung lysates [(1.00±0.15) vs.(5.14±0.42),P<0.001]. Moreover, FGF2 protein abundance was positively correlated with serum total and anti-HDM IgE levels in the HDM-induced chronic asthma model(R^(2)=0.857 and 0.783, P=0.0008 and 0.0043, respectively). Elevated FGF2protein was mainly expressed in asthmatic bronchial epithelium and alveolar areas and partly co-localised with infiltrated inflammatory cell populations in HDM-induced asthmatic mice. More importantly, intranasal instillation of rm-FGF2 aggravated airway inflammatory cell infiltration [(2.45±0.09) vs.(2.88±0.14), P=0.0288] and recruited more subepithelial neutrophils after HDM challenge [(110.20±29.43) cells/mm^(2) vs.(238.10±42.77) cells/mm^(2), P=0.0392]without affecting serum IgE levels and Th2 cytokine transcription. In A549 cells, FGF2 was upregulated through HDM stimulation and promoted IL-1β-induced IL-6 or IL-8 release levels [up to(1.41±0.12)-or(1.44±0.14)-fold change vs.IL-1β alone groups, P=0.001 or 0.0344, respectively]. The pro-inflammatory effect of FGF2 is likely mediated through the fibroblast growth factor receptor(FGFR)/mitogen-activated protein kinase(MAPK)/nuclear factor kappa B(NF-κB)pathway.Conclusions: Our findings suggest that FGF2 is a potential inflammatory modulator in asthma, which can be induced by HDM and acts through the FGFR/MAPK/NF-κB pathway in the airway epithelial cells.展开更多
Objective:To investigate the mechanism of regulation of airway neurogenic inflammation by Qiaoqin Qingfei agent in rats with cough variant asthma(CVA).Methods:48 SD rats were randomly divided into blank group,model gr...Objective:To investigate the mechanism of regulation of airway neurogenic inflammation by Qiaoqin Qingfei agent in rats with cough variant asthma(CVA).Methods:48 SD rats were randomly divided into blank group,model group,montelukast sodium group(1.05 mg/kg)and high,medium and low dose groups(26,13,6.5 g/kg),with 8 rats in each group.The rat CVA model was established by the method of ovalbumin(OVA)combined with aluminum hydroxide(Al(OH)3)sensitization and repeated stimulation.From the second day of sensitization,the rat CVA model was given by gavage for 28 days.The pathological changes of lung tissue were observed under microscope by HE staining.The content changes of nerve growth factor(NGF)and substance P(SP)in alveolar lavage fluid(BALF)were determined by double-antibody sandwich ABC-ELISA,and the protein expression levels of NGF and SP in lung tissue were detected by immunohistochemistry.Results:Pathological findings showed significant inflammatory manifestations in the model group,and the inflammatory infiltration in the high-dose,medium-dose and low-dose groups of Qiaoqin Qingfei agent and montelukast sodium groups were alleviated to varying degrees.Compared with blank group,the protein expression levels of NGF and SP in lung tissue of model group were significantly increased(P<0.01).Compared with model group,the protein expression levels of NGF and SP in lung tissue and the contents of NGF and SP in alveolar lavage fluid in high-dose,medium-dose and low-dose groups and montelukast sodium group were significantly decreased(P<0.05).Conclusion:Qiaoqin Qingfei agent may reduce airway inflammation and relieve cough variant asthma by regulating the protein expression levels of NGF and SP in airway neurogenic inflammation.展开更多
OBJECTIVE:To study the effects and mechanism of Shenqihuatan formula(参七化痰方,SQHT)of the transforming growth factor-beta(TGF-β)-stimulated cell processes in airway remodeling.METHODS:The current study examined cel...OBJECTIVE:To study the effects and mechanism of Shenqihuatan formula(参七化痰方,SQHT)of the transforming growth factor-beta(TGF-β)-stimulated cell processes in airway remodeling.METHODS:The current study examined cell viability using a Cell Counting Kit-8 assay.Furthermore,a Transwell assay was conducted to detect the ability of cell migration,and apoptosis was detected via flowcytometry.Western Blot and quantitative real-time polymerase chain reaction(q RT-PCR)were used to determine the expression levels of apoptosis or inflammation-related factors,such as TGF-β,Interleukin-1β(IL-1β),B cell lymphoma 2(Bcl-2),Bcl-2-Associated X(Bax),Ras homolog gene family,member A(Rho A),recombinant rho associated coiled coil containing protein kinase 1/2(ROCK1/2),extracellular regulated protein kinases 1/2(ERK1/2),Snail,and Slug.Finally,the expression levels of matrix metalloproteinase-9(MMP-9)and Tissue inhibitor of metalloproteinase(TIMP-1)were admeasured by enzyme-linked immuno sorbent assay.RESULTS:The results demonstrated that SQHT inhibited the viability and migration,as well as the the F-actin formation and cytoskeletal reorganization of airway smooth muscle cells(ASMCs)stimulated by TGF-β.By monitoring the changes of critical regulators in the presence of the formula,it was observed that the expression levels of TGF-β,IL-1β,Bcl-2,Rho A,ROCK1/2,ERK1/2,Snail,and Slug were markedly suppressed,whereas Bax expression exhibited the opposite effect.Compared with a well-characterized Rho A pathway inhibitor,Fasudil,SQHT generated equivalent or even higher inhibitory effects on these processes in ASMCs.CONCLUSIONS:Collectively,these suggested that SQHT can reduce airway inflammation by inhibiting TGF-β-stimulated signaling pathways in ASMCs.These findings may provide a novel remedy for treating ASMC inflammation,which causes thickening and obstruction of the airway in chronic obstructive pulmonary disease.展开更多
Aeroallergen sensitization,mainly mediated by lung epithelium and dendritic cells(DCs),is integral to allergic asthma pathogenesis and progression.IL-10 has a dual role in immune responses,as it inhibits myeloid cell ...Aeroallergen sensitization,mainly mediated by lung epithelium and dendritic cells(DCs),is integral to allergic asthma pathogenesis and progression.IL-10 has a dual role in immune responses,as it inhibits myeloid cell activation but promotes B-cell responses and epithelial cell proliferation.Here,we report a proinflammatory function of B-cell-derived IL-10 modulated by Bcl-3 in allergic asthma.Specifically,Bcl-3^(−/−)mice showed elevated IL-10 levels and were found to be highly vulnerable to allergic asthma induced by house dust mites(HDMs).IL-10 had a positive correlation with the levels of the DC chemoattractant CCL-20 in HDM-sensitized mice and in patients with asthma and induced a selective increase in CCL-20 production by mouse lung epithelial cells.Blockade of IL-10 or IL-10 receptors during sensitization dampened both HDM-induced sensitization and asthma development.IL-10 levels peaked 4 h post sensitization with HDM and IL-10 was primarily produced by B cells under Bcl-3–Blimp-1–Bcl-6 regulation.Mice lacking B-cell-derived IL-10 displayed decreased lung epithelial CCL-20 production and diminished DC recruitment to the lungs upon HDM sensitization,thereby demonstrating resistance to HDM-induced asthma.Moreover,responses to HDM stimulation in Bcl-3^(−/−)mice lacking B-cell-derived IL-10 were comparable to those in Bcl-3^(+/+)mice.The results revealed an unexpected role of B-cell-derived IL-10 in promoting allergic sensitization and demonstrated that Bcl-3 prevents HDM-induced asthma by inhibiting B-cell-derived IL-10 production.Thus,targeting the Bcl-3/IL-10 axis to inhibit allergic sensitization is a promising approach for treating allergic asthma.展开更多
Placental growth factor(PlGF)is a glycosylated dimeric protein that is homologous to vascular endothelial growth factor(VEGF).PlGF expression is upregulated in patients with bronchial asthma,suggesting that it plays a...Placental growth factor(PlGF)is a glycosylated dimeric protein that is homologous to vascular endothelial growth factor(VEGF).PlGF expression is upregulated in patients with bronchial asthma,suggesting that it plays a role in the pathogenesis of asthma.Bronchial asthma is characterized by chronic airway inflammation and airway hyperresponsiveness(AHR).After recurrent asthma attacks,pulmonary fibrosis develops and leads to airway remo-deling and a further decline in lung function.In this review,we focused on the pivotal role of PlGF in chronic airway inflammation,AHR,and airway remodeling during bronchial asthma.Furthermore,we summarized data showing that PlGF may be a potential therapeutic target in bronchial asthma.展开更多
Many inflammatory diseases are not curable,necessitating a better understanding of their pathobiology that may help identify novel biological targets.RhoA and Cdc42 of Rho family small GTPases regulate a variety of ce...Many inflammatory diseases are not curable,necessitating a better understanding of their pathobiology that may help identify novel biological targets.RhoA and Cdc42 of Rho family small GTPases regulate a variety of cellular functions such as actin cytoskeletal organization,cell adhesion,migration,proliferation,and survival.Recent characterization of mouse models of conditional gene knockout of RhoA and Cdc42 has revealed their physiological and cell type-specific roles in a number of cell types.In T lymphocytes,which play an important role in the pathogenesis of most,if not all,of the inflammatory diseases,we and others have investigated the effects of T cell-specific knockout of RhoA and Cdc42 on T cell development in the thymus,peripheral T cell homeostasis,activation,and differentiation to effector and regulatory T cells,and on T cell-mediated allergic airway inflammation and colitis.Here we highlight the phenotypes resulting from RhoA and Cdc42 deletion in T cells and discuss whether pharmacological targeting of RhoA and Cdc42 is feasible in treating asthma that is driven by allergic airway inflammation and colitis.展开更多
基金supported by the National Natural Science Foundation of China(No.81970024).
文摘Objective To observe effects of medication use on small airway function,airway inflammation and acute exacerbations in patients with clinically controlled asthma.Methods Forced expiratory flow over the middle half of the forced expiratory curve(FEF25%–75%),percentage of eosinophil,concentrations of eosinophil cationic protein(ECP)and interleukin(IL)-5 in induced sputum were assessed in patients with clinically controlled asthma who were given oral anti-inflammatory agents alone or in combination with inhaled therapy and inhaled therapy alone.Subsequently,acute exacerbations were compared between two groups during the 24-week follow-up period.Results FEF25%–75%in 43 patients with clinically controlled asthma given oral anti-inflammatory agents alone or in combination with inhaled therapy was significantly higher than that in 49 patients given inhaled therapy alone.Meanwhile,the percentage of eosinophils and levels of IL-5 and ECP in patients with clinically controlled asthma given oral anti-inflammatory agents alone or in combination with inhaled therapy were significantly lower than those in patients given inhaled therapy alone.Additionally,the patients with clinically controlled asthma given inhaled therapy were likely to have more acute exacerbation than the patients given oral anti-inflammatory agents alone or in combination with inhaled therapy during the 24-week follow-up period.Conclusion Systemic anti-inflammatory agents may have a greater effect on parameters reflecting small airway patency and reducing acute exacerbations,presumably secondary to reduction in airway inflammation.
基金Sichuan provincial cadre health-care project(2017-1601)Nanchong municipal strategic cooperation projects in science and technology(18SXHZ0301,18SXHZ0300)
文摘Objective:To observe the effect of vitaminD3 on airway inflammation and osteopontin(OPN)expression on cough variant asthma(CVA)models.Methods:SD rats were randomly divided into blank group,model group and treatment group,each group with 10 rats.The CVA model was induced by intraperitoneal injection combined with aerosolized ovalbumin(OVA),the treatment group was given 100 mg/ml of vitaminD330 minutes before challenge by administered orally.Airway hyperreaction were measured by airway resistance after inhalation of acetylcholine(Ach).Wright-Gimsa staining was used to observe the inflammatory cells in bronchoalveolar lavage fluid(BALF).HE and PAS were used to observe the morphological changes of lung tissue.OPN expression was detected by immunohistochemistry.Results:1)Airway hyperreaction:airway resistance after inhalation Ach in model group and treatment group were significantly higher than that in blank group(P<0.01),airway resistance in treatment group were lower than that in model group(P<0.01);2)Classification of inflammatory cells:The percentage of macrophages,lymphocytes,neutrophils,and eosinophils in the BALF of the model group and the treatment group were increased compared with the blank group(P<0.01),furthermore,the number of treatment group were lower than the model group(P<0.05);3)Morphological changes of lung tissue:a large amount of inflammatory cells and goblet cell proliferation were observed in the lung tissue of the model group,and these changes were slight in treatment group compared with model group;OPN expression in lung tissue:The expression of OPN in model and treatment group were increased compared with blank group(P<0.05),and the treatment group was lower than that of model group(P<0.05).The OPN content was positively correlated with the percentage of inflammatory cells in BALF(P<0.05).Conclusions:Vitamin D3 can reduce airway hyperreaction and airway inflammation in CVA rats.The mechanism may be related to the intervention of OPN expression in lung tissue.
基金Construction Project for Famous Doctors of Traditional Chinese Medicine of Ruikang Hospital Affiliated to Guangxi University of Traditional Chinese Medicine(No.[2019]18)。
文摘Objective:To investigate the effect of Fufei Gushen Decoction on airway inflammation and glucocorticoid receptor in rats with chronic obstructive pulmonary disease.Methods:Fifty Wistar male rats were randomly divided into 5 groups:blank control group,COPD model group,Fufei Gushen Yin high,medium and low dose groups,10 rats in each group,except the blank control group,the remaining 4 groups were Smoked combined with lipopolysaccharide(LPS),cold air stimulation to create CODP rat model.After successful modeling,the blank control group and COPD model group were fed with distilled water 3ml/only,Fufei Gushen Yin high,medium and low dose groups were given 1.02,0.51,0.26g Chinese medicine granules/100g/day,respectively.2 times a day for 28 consecutive days.Samples were collected,hematoxylin-eosin(HE)staining was used to observe the pathological changes of lung tissue,and enzyme-linked immunosorbent assay(ELISA)was used to detect the tumor necrosis factor alpha(TNF-α)in the serum and right alveolar lavage fluid(BALF)of rats in each group.),the content of transforming growth factorβ1(TGF-β1),interleukin-17(IL-17A)and matrix metalloproteinase(MMP-9)and tissue inhibitor of metalloproteinase-1(TIMP-1)in the left lung tissue The expression level of real-time fluorescence quantitative polymerase chain reaction(Real-time PCR)rat left lung tissue GRmRNA,immunohistochemistry(IHC)to determine the expression level of left lung tissue glucocorticoid receptor(GR).Results:The content of TNF-α,TGF-β1 and IL-17A in the serum of COPD rats in Fufei Gushen Yin high,medium and low dose groups and BALF were significantly reduced compared with the COPD model group(P<0.05);The expressions of TIMP-1 and MMP-9 in tissues were lower than those in COPD model group(P<0.05);the expressions of GRmRNA and GR in lung tissues were higher than those in COPD model group(P<0.05),and were higher in Fufei Gushen Yin Among the middle-and low-dose groups,the middle-dose group has the most significant effect.Conclusion:Fufei Gushen Decoction can inhibit the release of inflammatory factors in lung tissue of COPD rats,improve airway inflammation and remodeling,and increase hormone sensitivity.
基金supported by grants from the National Natural Science Foundation of China for Young Scholar(No.81801484)China Postdoctoral Science Foundation(No.2014M552369)+1 种基金Natural Science Foundation of Guangdong Province(No.2017A030310286)Scientific Research Project of Guangzhou(No.201707010282)。
文摘Background:Mounting evidence,consistent with our previous study,showed thatγ-aminobutyric acid type A receptor(GABAAR)played an indispensable role in airway inflammation and mucus hypersecretion in asthma.Monocyte chemotactic protein-inducing protein 1(MCPIP1)was a key negative regulator of inflammation.Recent studies showed that inflammation was largely suppressed by enhanced MCPIP1 expression in many inflammatory diseases.However,the role and potential mechanism of MCPIP1 in airway inflammation and mucus hypersecretion in asthma were still not well studied.This study was to explore the role of MCPIP1 in asthmatic airway inflammation and mucus hypersecretion in both mice and BEAS-2B cells,and its potential mechanism.Methods:In vivo,mice were sensitized and challenged by ovalbumin(OVA)to induce asthma.Airway inflammation and mucus secretion were analyzed.In vitro,BEAS-2B cells were chosen.Interleukin(IL)-13 was used to stimulate inflammation and mucus hypersecretion in cells.MCPIP1 Lentiviral vector(LA-MCPIP1)and plasmid-MCPIP1 were used to up-regulate MCPIP1 in lung and cells,respectively.MCP-1,thymic stromal lymphopoietin(TSLP),mucin 5AC(MUC5AC),MCPIP1,and GABAARβ2 expressions were measured in both lung and BEAS-2B cells.Immunofluorescence staining was performed to observe the expression of GABAARβ2 in cells.Results:MCPIP1 was up-regulated by LA-MCPIP1(P<0.001)and plasmid-MCPIP1(P<0.001)in lung and cells,respectively.OVA-induced airway inflammation and mucus hypersecretion,OVA-enhanced MCP-1,TSLP,MUC5AC,and GABAARβ2 expressions,and OVA-reduced MCPIP1 were significantly blunted by LA-MCPIP1 in mice(all P<0.001).IL-13-enhanced MCP-1,TSLP,MUC5AC,and GABAARβ2 expressions,and IL-13-reduced MCPIP1 were markedly abrogated by plasmid-MCPIP1 in BEAS-2B cells(all P<0.001).Conclusion:The results of this study suggested that OVA and IL-13-induced airway inflammation and mucus hypersecretion were negatively regulated by MCPIP1 in both lung and BEAS-2B cells,involving GABAAR signaling pathway.
基金by grants 91542103 and 31770994 from the National Natural Science Foundation of China(to J.H.)grant 2015CFB620 from the Natural Science Foundation of Hubei Province(to J.H.).
文摘Allergic asthma,a chronic inflammatory airway disease associated with type 2 cytokines,often originates in early life.Immune responses at an early age exhibit a Th2 cell bias,but the precise mechanisms remain elusive.Plasmacytoid dendritic cells(pDCs),which play a regulatory role in allergic asthma,were shown to be deficient in neonatal mice.We report here that this pDC deficiency renders neonatal mice more susceptible to severe allergic airway inflammation than adult mice in an OVA-induced experimental asthma model.Adoptive transfer of pDCs or administration of IFN-αto neonatal mice prevented the development of allergic inflammation in wild type but not in IFNAR1−/−mice.Similarly,adult mice developed more severe allergic inflammation when pDCs were depleted.The protective effects of pDCs were mediated by the pDC-/IFN-α-mediated negative regulation of the secretion of epithelial cell-derived CCL20,GM-CSF,and IL-33,which in turn impaired the recruitment of cDC2 and ILC2 cells to the airway.In asthmatic patients,the percentage of pDCs and the level of IFN-αwere lower in children than in adults.These results indicate that impairment of pDC-epithelial cell crosstalk in neonates is a susceptibility factor for the development of allergeninduced allergic airway inflammation.
基金This work was supported by the following grants:National Natural Science Foundation of China(Nos.31671424,91749108,and 81322004 to Heng MaNo.81200036 to Manling Liu)+1 种基金the Science and Technology Research and Development Program of Shaanxi Province,China(No.2015KW-050 to Heng Ma,No.2019SF-008 to Manling Liu,and No.2018SF-101 to Nan Mu)the Youth Innovation Team of Shaanxi Universities,China(to Heng Ma,Yue Yin,Nan Mu,Yishi Wang).
文摘Exposure to particulate matter 2.5(PM2.5)potentially triggers airway inflammation by activating nuclear factor-κB(NF-κB).Sirtuin 2(SIRT2)is a key modulator in inflammation.However,the function and specific mechanisms of SIRT2 in PM2.5-induced airway inflammation are largely understudied.Therefore,this work investigated the mechanisms of SIRT2 in regulating the phosphorylation and acetylation of p65 influenced by PM2.5-induced airway inflammation and bronchial hyperresponsiveness.Results revealed that PM2.5 exposure lowered the expression and activity of SIRT2 in bronchial tissues.Subsequently,SIRT2 impairment promoted the phosphorylation and acetylation of p65 and activated the NF-κB signaling pathway.The activation of p65 triggered airway inflammation,increment of mucus secretion by goblet cells,and acceleration of tracheal stenosis.Meanwhile,p65 phosphorylation and acetylation,airway inflammation,and bronchial hyperresponsiveness were deteriorated in SIRT2 knockout mice exposed to PM2.5.Triptolide(a specific p65 inhibitor)reversed p65 activation and ameliorated PM2.5-induced airway inflammation and bronchial hyperresponsiveness.Our findings provide novel insights into the molecular mechanisms underlying the toxicity of PM2.5 exposure.Triptolide inhibition of p65 phosphorylation and acetylation could be an effective therapeutic approach in averting PM2.5-induced airway inflammation and bronchial hyperresponsiveness.
基金This work was supported by grants from the National Natural Science Foundation of China(32188101,31830024 and 32070775)the CAMS Innovation Fund for Medical Sciences(2019-I2M-5-071)the Fundamental Research Funds for the Central Universities.
文摘Interleukin 5(IL-5)plays crucial roles in type 2-high asthma by mediating eosinophil maturation,activation,chemotaxis and survival.Inhibition of IL-5 signaling is considered a strategy for asthma treatment.Here,we identified MARCH2 and MARCH3 as critical negative regulators of IL-5-triggered signaling.MARCH2 and MARCH3 associate with the IL-5 receptorαchain(IL-5Rα)and mediate its K27-linked polyubiquitination at K379 and K383,respectively,and its subsequent lysosomal degradation.Deficiency of MARCH2 or MARCH3 modestly increases the level of IL-5Rαand enhances IL-5-induced signaling,whereas double knockout of MARCH2/3 has a more dramatic effect.March2/3 double knockout markedly increases the proportions of eosinophils in the bone marrow and peripheral blood in mice.Double knockout of March2/3 aggravates ovalbumin(OVA)-induced eosinophilia and causes increased inflammatory cell infiltration,peribronchial mucus secretion and production of Th2 cytokines.Neutralization of Il-5 attenuates OVA-induced airway inflammation and the enhanced effects of March2/3 double deficiency.These findings suggest that MARCH2 and MARCH3 play redundant roles in targeting IL-5Rαfor degradation and negatively regulating allergic airway inflammation.
文摘Objective To investigate the effects of 3-methyladenineon airway inflammation,airway hyperresponsivenessand mucus secretion in asthmatic mice,and to explore itsmechanism. Methods C57BL /6J female mice were randomlydivided into normal control group ( PBS),OVAgroup(OVA),OVA with 3-methyladenine group (OVA +3-MA),and OVA with 4-phenylbutyrate group (OVA +4-PBA). OVA group,OVA + 3-MA group and OVA + 4-PBA groups were all sensitized and challenged with OVAto establish asthmatic models,while PBS group was givenPBS as a control. At 2 h before challenge,OVA + 3-MAgroup was intraperitoneally injected with 3-methyladenine,and OVA + 4-PBA group was intraperitoneally injectedwith 4-phenylbutyrate. Airway hyperresponsiveness,eosinophils,and pathological changes of pulmonarytissue (hematoxylin-eosin,HE staining) were measuredto confirm the establishment of asthmatic models.
基金supported by grants awarded to YY by the National Natural Science Foundation of China (81870019, 82170029)the Guangdong Provincial Natural Science Foundation (2018A030313554)+3 种基金the Innovation Research Team for Basic and Clinical Studies on Chronic Liver Diseases of 2018 High-Level Health Teams of ZhuhaiYKQ by the National Natural Science Foundation of China (82002612)the Chinese Postdoctoral Science Foundation (2019M660211)ZGC by the Science and Technology Program of Guangzhou,China (201704020179)。
文摘Background: Airway inflammation is the core pathological process of asthma, with the key inflammatory regulators incompletely defined. Recently, fibroblast growth factor 2(FGF2) has been reported to be an inflammatory regulator;however, its role in asthma remains elusive. This study aimed to investigate the immunomodulatory role of FGF2 in asthma.Methods: First, FGF2 expression was characterised in clinical asthma samples and the house dust mite(HDM)-induced mouse chronic asthma model. Second, recombinant mouse FGF2(rm-FGF2) protein was intranasally delivered to determine the effect of FGF2 on airway inflammatory cell infiltration. Third, human airway epithelium-derived A549 cells were stimulated with either HDM or recombinant human interleukin-1β(IL-1β) protein combined with or without recombinant human FGF2. IL-1β-induced IL-6 or IL-8 release levels were determined using enzyme-linked immunosorbent assay, and the involved signalling transduction was explored via Western blotting.Results: Compared with the control groups, the FGF2 protein levels were significantly upregulated in the bronchial epithelium and alveolar areas of clinical asthma samples [(6.70±1.79) vs.(16.32±2.40), P=0.0184;(11.20±2.11) vs.(21.00±3.00), P=0.033, respectively] and HDM-induced asthmatic mouse lung lysates [(1.00±0.15) vs.(5.14±0.42),P<0.001]. Moreover, FGF2 protein abundance was positively correlated with serum total and anti-HDM IgE levels in the HDM-induced chronic asthma model(R^(2)=0.857 and 0.783, P=0.0008 and 0.0043, respectively). Elevated FGF2protein was mainly expressed in asthmatic bronchial epithelium and alveolar areas and partly co-localised with infiltrated inflammatory cell populations in HDM-induced asthmatic mice. More importantly, intranasal instillation of rm-FGF2 aggravated airway inflammatory cell infiltration [(2.45±0.09) vs.(2.88±0.14), P=0.0288] and recruited more subepithelial neutrophils after HDM challenge [(110.20±29.43) cells/mm^(2) vs.(238.10±42.77) cells/mm^(2), P=0.0392]without affecting serum IgE levels and Th2 cytokine transcription. In A549 cells, FGF2 was upregulated through HDM stimulation and promoted IL-1β-induced IL-6 or IL-8 release levels [up to(1.41±0.12)-or(1.44±0.14)-fold change vs.IL-1β alone groups, P=0.001 or 0.0344, respectively]. The pro-inflammatory effect of FGF2 is likely mediated through the fibroblast growth factor receptor(FGFR)/mitogen-activated protein kinase(MAPK)/nuclear factor kappa B(NF-κB)pathway.Conclusions: Our findings suggest that FGF2 is a potential inflammatory modulator in asthma, which can be induced by HDM and acts through the FGFR/MAPK/NF-κB pathway in the airway epithelial cells.
基金Research Project of Guangdong Provincial Bureau of Traditional Chinese Medicine(No.20222183,20221320)Guangzhou Traditional Chinese Medicine and Integrated Traditional Chinese and Western Medicine Technology Project(No.20222A010020)。
文摘Objective:To investigate the mechanism of regulation of airway neurogenic inflammation by Qiaoqin Qingfei agent in rats with cough variant asthma(CVA).Methods:48 SD rats were randomly divided into blank group,model group,montelukast sodium group(1.05 mg/kg)and high,medium and low dose groups(26,13,6.5 g/kg),with 8 rats in each group.The rat CVA model was established by the method of ovalbumin(OVA)combined with aluminum hydroxide(Al(OH)3)sensitization and repeated stimulation.From the second day of sensitization,the rat CVA model was given by gavage for 28 days.The pathological changes of lung tissue were observed under microscope by HE staining.The content changes of nerve growth factor(NGF)and substance P(SP)in alveolar lavage fluid(BALF)were determined by double-antibody sandwich ABC-ELISA,and the protein expression levels of NGF and SP in lung tissue were detected by immunohistochemistry.Results:Pathological findings showed significant inflammatory manifestations in the model group,and the inflammatory infiltration in the high-dose,medium-dose and low-dose groups of Qiaoqin Qingfei agent and montelukast sodium groups were alleviated to varying degrees.Compared with blank group,the protein expression levels of NGF and SP in lung tissue of model group were significantly increased(P<0.01).Compared with model group,the protein expression levels of NGF and SP in lung tissue and the contents of NGF and SP in alveolar lavage fluid in high-dose,medium-dose and low-dose groups and montelukast sodium group were significantly decreased(P<0.05).Conclusion:Qiaoqin Qingfei agent may reduce airway inflammation and relieve cough variant asthma by regulating the protein expression levels of NGF and SP in airway neurogenic inflammation.
基金Supported by the General Program of National Natural Science Foundation of China:Study on the Mechanism of the Method of Yiqi Huoxue Huata regulating autophagy in airway epithelial cells of COPD based on SIRT1/mTOR signaling pathway(No.82174312)and Study on the mechanism of the method of YIQI HUOXUE HUATA intervention in COPD airway remodeling based on RhoA/ROCK signaling pathway(No.81473675)
文摘OBJECTIVE:To study the effects and mechanism of Shenqihuatan formula(参七化痰方,SQHT)of the transforming growth factor-beta(TGF-β)-stimulated cell processes in airway remodeling.METHODS:The current study examined cell viability using a Cell Counting Kit-8 assay.Furthermore,a Transwell assay was conducted to detect the ability of cell migration,and apoptosis was detected via flowcytometry.Western Blot and quantitative real-time polymerase chain reaction(q RT-PCR)were used to determine the expression levels of apoptosis or inflammation-related factors,such as TGF-β,Interleukin-1β(IL-1β),B cell lymphoma 2(Bcl-2),Bcl-2-Associated X(Bax),Ras homolog gene family,member A(Rho A),recombinant rho associated coiled coil containing protein kinase 1/2(ROCK1/2),extracellular regulated protein kinases 1/2(ERK1/2),Snail,and Slug.Finally,the expression levels of matrix metalloproteinase-9(MMP-9)and Tissue inhibitor of metalloproteinase(TIMP-1)were admeasured by enzyme-linked immuno sorbent assay.RESULTS:The results demonstrated that SQHT inhibited the viability and migration,as well as the the F-actin formation and cytoskeletal reorganization of airway smooth muscle cells(ASMCs)stimulated by TGF-β.By monitoring the changes of critical regulators in the presence of the formula,it was observed that the expression levels of TGF-β,IL-1β,Bcl-2,Rho A,ROCK1/2,ERK1/2,Snail,and Slug were markedly suppressed,whereas Bax expression exhibited the opposite effect.Compared with a well-characterized Rho A pathway inhibitor,Fasudil,SQHT generated equivalent or even higher inhibitory effects on these processes in ASMCs.CONCLUSIONS:Collectively,these suggested that SQHT can reduce airway inflammation by inhibiting TGF-β-stimulated signaling pathways in ASMCs.These findings may provide a novel remedy for treating ASMC inflammation,which causes thickening and obstruction of the airway in chronic obstructive pulmonary disease.
基金We thank Dr.Mingfang Lu,Dr.Wei Jiang,Dr.Guohong Hu,Dr.Jin Li,and Dr.Xubo Huang for providing advice as well as some reagents used in this study.We appreciate Dr.Michael Reth and Dr.Axel Roers for gifting Il10fl/fl and Mb1-Cre mice.This investigation was funded by the National Natural Science Foundation of China(grants 81901633 to GQ and 91949102 to XZ)the National Program on Key Research(2021YFA0804703 to XZ)the Discipline Construction Projects of Guangzhou Medical University(02-445-2301246XM to XZ).
文摘Aeroallergen sensitization,mainly mediated by lung epithelium and dendritic cells(DCs),is integral to allergic asthma pathogenesis and progression.IL-10 has a dual role in immune responses,as it inhibits myeloid cell activation but promotes B-cell responses and epithelial cell proliferation.Here,we report a proinflammatory function of B-cell-derived IL-10 modulated by Bcl-3 in allergic asthma.Specifically,Bcl-3^(−/−)mice showed elevated IL-10 levels and were found to be highly vulnerable to allergic asthma induced by house dust mites(HDMs).IL-10 had a positive correlation with the levels of the DC chemoattractant CCL-20 in HDM-sensitized mice and in patients with asthma and induced a selective increase in CCL-20 production by mouse lung epithelial cells.Blockade of IL-10 or IL-10 receptors during sensitization dampened both HDM-induced sensitization and asthma development.IL-10 levels peaked 4 h post sensitization with HDM and IL-10 was primarily produced by B cells under Bcl-3–Blimp-1–Bcl-6 regulation.Mice lacking B-cell-derived IL-10 displayed decreased lung epithelial CCL-20 production and diminished DC recruitment to the lungs upon HDM sensitization,thereby demonstrating resistance to HDM-induced asthma.Moreover,responses to HDM stimulation in Bcl-3^(−/−)mice lacking B-cell-derived IL-10 were comparable to those in Bcl-3^(+/+)mice.The results revealed an unexpected role of B-cell-derived IL-10 in promoting allergic sensitization and demonstrated that Bcl-3 prevents HDM-induced asthma by inhibiting B-cell-derived IL-10 production.Thus,targeting the Bcl-3/IL-10 axis to inhibit allergic sensitization is a promising approach for treating allergic asthma.
基金supported by the National Science Foundation of Guangdong Province,China(No.2022A1515011731,2021A1515011062)Guangdong Provincial Administration of Traditional Chinese Medicine(China)(No.20221211)+1 种基金Project of Zhanjiang City,Guangdong,China(No.2020A01016,2020B01346,2021A05077,2016B01062)Affiliated Hospital of Guangdong Medical University(China)(No.4SG21231G,LCYJ2017A003,CLP202113001,CLP2021B001,LCYJ2020B008,BK201616).
文摘Placental growth factor(PlGF)is a glycosylated dimeric protein that is homologous to vascular endothelial growth factor(VEGF).PlGF expression is upregulated in patients with bronchial asthma,suggesting that it plays a role in the pathogenesis of asthma.Bronchial asthma is characterized by chronic airway inflammation and airway hyperresponsiveness(AHR).After recurrent asthma attacks,pulmonary fibrosis develops and leads to airway remo-deling and a further decline in lung function.In this review,we focused on the pivotal role of PlGF in chronic airway inflammation,AHR,and airway remodeling during bronchial asthma.Furthermore,we summarized data showing that PlGF may be a potential therapeutic target in bronchial asthma.
基金This work was supported in part by the National Institutes of Health(Grant No.R01CA234038).
文摘Many inflammatory diseases are not curable,necessitating a better understanding of their pathobiology that may help identify novel biological targets.RhoA and Cdc42 of Rho family small GTPases regulate a variety of cellular functions such as actin cytoskeletal organization,cell adhesion,migration,proliferation,and survival.Recent characterization of mouse models of conditional gene knockout of RhoA and Cdc42 has revealed their physiological and cell type-specific roles in a number of cell types.In T lymphocytes,which play an important role in the pathogenesis of most,if not all,of the inflammatory diseases,we and others have investigated the effects of T cell-specific knockout of RhoA and Cdc42 on T cell development in the thymus,peripheral T cell homeostasis,activation,and differentiation to effector and regulatory T cells,and on T cell-mediated allergic airway inflammation and colitis.Here we highlight the phenotypes resulting from RhoA and Cdc42 deletion in T cells and discuss whether pharmacological targeting of RhoA and Cdc42 is feasible in treating asthma that is driven by allergic airway inflammation and colitis.
