BACKGROUND Acute pancreatitis(AP)is an inflammatory disease in which the regulatory pathway is complex and not well understood.Soluble suppression of tumorigenicity 2(sST2)protein receptor functions as a decoy recepto...BACKGROUND Acute pancreatitis(AP)is an inflammatory disease in which the regulatory pathway is complex and not well understood.Soluble suppression of tumorigenicity 2(sST2)protein receptor functions as a decoy receptor for interleukin(IL)-33 to prevent IL-33/suppression of tumorigenicity 2L(ST2L)-pathwaymediated T helper(Th)2 immune responses.AIM To investigate the role of sST2 in AP.METHODS We assessed the association between sST2 and severity of AP in 123 patients enrolled in this study.The serum levels of sST2,C-reactive protein(CRP)and Th1-and Th2-related cytokines,including interferon(IFN)-γ,tumor necrosis factor(TNF)-α,IL-2,IL-4,IL-5 and IL-13,were measured by highly sensitive ELISA,and the severity of AP in patients was evaluated by the 2012 Atlanta Classification Criteria.RESULTS Serum sST2 levels were significantly increased in AP patients,and further,these levels were significantly elevated in severe AP(SAP)patients compared to moderately severe AP(MSAP)and mild AP(MAP)patients.Logistic regression showed sST2 was a predictor of SAP[odds ratio(OR):1.003(1.001–1.006),P=0.000].sST2 cutoff point was 1190 pg/mL,and sST2 above this cutoff was associated with SAP.sST2 was also a predictor of any organ failure and mortality during AP[OR:1.006(1.003–1.009),P=0.000,OR:1.002(1.001–1.004),P=0.012,respectively].Additionally,the Th1-related cytokines IFN-γand TNF-αin the SAP group were higher and the Th2-related cytokine IL-4 in the SAP group was significantly lower than those in MSAP and MAP groups.CONCLUSION sST2 may be used as a novel inflammatory marker in predicting AP severity and may regulate the function and differentiation of IL-33/ST2-mediated Th1 and Th2 Lymphocytes in AP homeostasis.展开更多
BACKGROUND Acute lung injury(ALI)is a common and life-threatening complication of severe acute pancreatitis(SAP).There are currently limited effective treatment options for SAP and associated ALI.Calycosin(Cal),a bioa...BACKGROUND Acute lung injury(ALI)is a common and life-threatening complication of severe acute pancreatitis(SAP).There are currently limited effective treatment options for SAP and associated ALI.Calycosin(Cal),a bioactive constituent extracted from the medicinal herb Radix Astragali exhibits potent anti-inflammatory properties,but its effect on SAP and associated ALI has yet to be determined.AIM To identify the roles of Cal in SAP-ALI and the underlying mechanism.METHODS SAP was induced via two intraperitoneal injections of L-arg(4 g/kg)and Cal(25 or 50 mg/kg)were injected 1 h prior to the first L-arg challenge.Mice were sacrificed 72 h after the induction of SAP and associated ALI was examined histologically and biochemically.An in vitro model of lipopolysaccharide(LPS)-induced ALI was established using A549 cells.Immunofluorescence analysis and western blot were evaluated in cells.Molecular docking analyses were conducted to examine the interaction of Cal with HMGB1.RESULTS Cal treatment substantially reduced the serum amylase levels and alleviated histopathological injury associated with SAP and ALI.Neutrophil infiltration and lung tissue levels of neutrophil mediator myeloperoxidase were reduced in line with protective effects of Cal against ALI in SAP.Cal treatment also attenuated the serum levels and mRNA expression of pro-inflammatory cytokines tumor necrosis factor-α,interleukin-6,IL-1β,HMGB1 and chemokine(CXC motif)ligand 1 in lung tissue.Immunofluorescence and western blot analyses showed that Cal treatment markedly suppressed the expression of HMGB1 and phosphorylated nuclear factor-kappa B(NF-κB)p65 in lung tissues and an in vitro model of LPSinduced ALI in A549 cells suggesting a role for HGMB1 in the pathogenesis of ALI.Furthermore,molecular docking analysis provided evidence for the direct interaction of Cal with HGMB1.CONCLUSION Cal protects mice against L-arg-induced SAP and associated ALI by attenuating local and systemic neutrophil infiltration and inflammatory response via inhibition of HGMB1 and the NF-κB signaling pathway.展开更多
基金Supported by Henan Province Education Department for Henan Province University Key Scientific Research Project,No.20A320018 and No.20A320064。
文摘BACKGROUND Acute pancreatitis(AP)is an inflammatory disease in which the regulatory pathway is complex and not well understood.Soluble suppression of tumorigenicity 2(sST2)protein receptor functions as a decoy receptor for interleukin(IL)-33 to prevent IL-33/suppression of tumorigenicity 2L(ST2L)-pathwaymediated T helper(Th)2 immune responses.AIM To investigate the role of sST2 in AP.METHODS We assessed the association between sST2 and severity of AP in 123 patients enrolled in this study.The serum levels of sST2,C-reactive protein(CRP)and Th1-and Th2-related cytokines,including interferon(IFN)-γ,tumor necrosis factor(TNF)-α,IL-2,IL-4,IL-5 and IL-13,were measured by highly sensitive ELISA,and the severity of AP in patients was evaluated by the 2012 Atlanta Classification Criteria.RESULTS Serum sST2 levels were significantly increased in AP patients,and further,these levels were significantly elevated in severe AP(SAP)patients compared to moderately severe AP(MSAP)and mild AP(MAP)patients.Logistic regression showed sST2 was a predictor of SAP[odds ratio(OR):1.003(1.001–1.006),P=0.000].sST2 cutoff point was 1190 pg/mL,and sST2 above this cutoff was associated with SAP.sST2 was also a predictor of any organ failure and mortality during AP[OR:1.006(1.003–1.009),P=0.000,OR:1.002(1.001–1.004),P=0.012,respectively].Additionally,the Th1-related cytokines IFN-γand TNF-αin the SAP group were higher and the Th2-related cytokine IL-4 in the SAP group was significantly lower than those in MSAP and MAP groups.CONCLUSION sST2 may be used as a novel inflammatory marker in predicting AP severity and may regulate the function and differentiation of IL-33/ST2-mediated Th1 and Th2 Lymphocytes in AP homeostasis.
文摘BACKGROUND Acute lung injury(ALI)is a common and life-threatening complication of severe acute pancreatitis(SAP).There are currently limited effective treatment options for SAP and associated ALI.Calycosin(Cal),a bioactive constituent extracted from the medicinal herb Radix Astragali exhibits potent anti-inflammatory properties,but its effect on SAP and associated ALI has yet to be determined.AIM To identify the roles of Cal in SAP-ALI and the underlying mechanism.METHODS SAP was induced via two intraperitoneal injections of L-arg(4 g/kg)and Cal(25 or 50 mg/kg)were injected 1 h prior to the first L-arg challenge.Mice were sacrificed 72 h after the induction of SAP and associated ALI was examined histologically and biochemically.An in vitro model of lipopolysaccharide(LPS)-induced ALI was established using A549 cells.Immunofluorescence analysis and western blot were evaluated in cells.Molecular docking analyses were conducted to examine the interaction of Cal with HMGB1.RESULTS Cal treatment substantially reduced the serum amylase levels and alleviated histopathological injury associated with SAP and ALI.Neutrophil infiltration and lung tissue levels of neutrophil mediator myeloperoxidase were reduced in line with protective effects of Cal against ALI in SAP.Cal treatment also attenuated the serum levels and mRNA expression of pro-inflammatory cytokines tumor necrosis factor-α,interleukin-6,IL-1β,HMGB1 and chemokine(CXC motif)ligand 1 in lung tissue.Immunofluorescence and western blot analyses showed that Cal treatment markedly suppressed the expression of HMGB1 and phosphorylated nuclear factor-kappa B(NF-κB)p65 in lung tissues and an in vitro model of LPSinduced ALI in A549 cells suggesting a role for HGMB1 in the pathogenesis of ALI.Furthermore,molecular docking analysis provided evidence for the direct interaction of Cal with HGMB1.CONCLUSION Cal protects mice against L-arg-induced SAP and associated ALI by attenuating local and systemic neutrophil infiltration and inflammatory response via inhibition of HGMB1 and the NF-κB signaling pathway.
