Interleukin 17(IL-17)and its main producer,T cell receptorγδcells,have neurotoxic effects in the pathogenesis of intracerebral hemorrhage(ICH),aggravating brain injuries.To investigate the correlation between IL-17 ...Interleukin 17(IL-17)and its main producer,T cell receptorγδcells,have neurotoxic effects in the pathogenesis of intracerebral hemorrhage(ICH),aggravating brain injuries.To investigate the correlation between IL-17 and ICH,we dynamically screened serum IL-17 concentrations using enzyme-linked immunosorbent assay and explored the clinical values of IL-17 in ICH patients.There was a significant negative correlation between serum IL-17 level and neurological recovery status in ICH patients(r=–0.498,P<0.01).To study the neurotoxic role of IL-17,C57 BL/6 mice were used to establish an ICH model by injecting autologous blood into the caudate nucleus.Subsequently,the mice were treated with mouse neural stem cells(NSCs)and/or IL-17 neutralizing antibody for 72 hours.Flow cytometry,brain water content detection,Nissl staining,and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling results indicated that NSC transplantation significantly reduced IL-17 expression in peri-hematoma tissue,but there was no difference in T cell receptorγδcells.Compared with the ICH group,there were fewer apoptotic bodies and more Nissl bodies in the ICH+NSC group and the ICH+NSC+IL-17 group.To investigate the potential effect of IL-17 on directional differentiation of NSCs,we cultured mouse NSCs(NE-4 C)alone or co-cultured them with T cell receptorγδcells,which were isolated from mouse peripheral blood mononuclear cells,for 7 days.The results of western blot assays revealed that IL-17 secreted by T cell receptorγδcells reduced the differentiation of NSCs into astrocytes and neurons,while IL-17 neutralization relieved the inhibition of directional differentiation into astrocytes rather than neurons.In conclusion,serum IL-17 levels were elevated in the early stage of ICH and were negatively correlated with outcome in ICH patients.Animal experiments and cytological investigations therefore demonstrated that IL-17 probably has neurotoxic roles in ICH because of its inhibitory effects on the directional differentiation of NSCs.The application of IL-17 neutralizing antibody may promote the directional differentiation of NSCs into astrocytes.This study was approved by the Clinical Research Ethics Committee of Anhui Medical University of China(For human study:Approval No.20170135)in December 2016.All animal handling and experimentation were reviewed and approved by the Institutional Animal Care and Use Committee of Anhui Medical University(approval No.20180248)in December 2017.展开更多
[Objectives]To explore the expression of interleukin 34(IL-34)in gastric adenocarcinoma tissues and its relationship with apoptosis of gastric adenocarcinoma cells.[Methods]60 cases of surgically resected human gastri...[Objectives]To explore the expression of interleukin 34(IL-34)in gastric adenocarcinoma tissues and its relationship with apoptosis of gastric adenocarcinoma cells.[Methods]60 cases of surgically resected human gastric adenocarcinoma tissue specimen and 50 cases of adjacent normal gastric mucosa tissue specimen were collected,and the expression of IL-34 protein was determined by immunohistochemical streptavidin-perosidase(SP)method.Cell apoptosis in tissue specimen was detected by TUNEL staining method,and the relationship between IL-34 protein expression and apoptosis of gastric adenocarcinoma cells was analyzed.[Results]Immunohistochemical SP experiment indicated that the expression of IL-34 protein in gastric adenocarcinoma was higher than that in adjacent normal gastric mucosa(P<0.05);its positive expression was related to histological differentiation,TNM stage,invasion depth,and lymph node metastasis of gastric adenocarcinoma(P<0.05),but not to gender and age(P>0.05).TUNEL experiment showed that compared with the adjacent normal gastric mucosa group,the apoptosis index(AI)of gastric adenocarcinoma group was significantly lower(P<0.05);the AI was related to histological differentiation,TNM stage,tumor invasion depth and lymph node metastasis of gastric adenocarcinoma(P<0.05),but not to gender and age(P>0.05).In gastric adenocarcinoma,the AI of IL-34 positive expression group was lower than that of IL-34 negative expression group,and the results were statistically significant(P<0.05).[Conclusions]IL-34 has high expression in gastric adenocarcinoma tissues and is negatively correlated with cancer cell apoptosis.Abnormal expression of IL-34 is involved in the occurrence and development of gastric adenocarcinoma.This provides a new idea for the pathogenesis research and clinical treatment of gastric adenocarcinoma.展开更多
基金supported by the Natural Science Foundation of Anhui Province of China,No.1708085MH211(to HWC)the College Top-notch Talent Foundation of Anhui Province of China,No.KJ2018A0207(to HWC)
文摘Interleukin 17(IL-17)and its main producer,T cell receptorγδcells,have neurotoxic effects in the pathogenesis of intracerebral hemorrhage(ICH),aggravating brain injuries.To investigate the correlation between IL-17 and ICH,we dynamically screened serum IL-17 concentrations using enzyme-linked immunosorbent assay and explored the clinical values of IL-17 in ICH patients.There was a significant negative correlation between serum IL-17 level and neurological recovery status in ICH patients(r=–0.498,P<0.01).To study the neurotoxic role of IL-17,C57 BL/6 mice were used to establish an ICH model by injecting autologous blood into the caudate nucleus.Subsequently,the mice were treated with mouse neural stem cells(NSCs)and/or IL-17 neutralizing antibody for 72 hours.Flow cytometry,brain water content detection,Nissl staining,and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling results indicated that NSC transplantation significantly reduced IL-17 expression in peri-hematoma tissue,but there was no difference in T cell receptorγδcells.Compared with the ICH group,there were fewer apoptotic bodies and more Nissl bodies in the ICH+NSC group and the ICH+NSC+IL-17 group.To investigate the potential effect of IL-17 on directional differentiation of NSCs,we cultured mouse NSCs(NE-4 C)alone or co-cultured them with T cell receptorγδcells,which were isolated from mouse peripheral blood mononuclear cells,for 7 days.The results of western blot assays revealed that IL-17 secreted by T cell receptorγδcells reduced the differentiation of NSCs into astrocytes and neurons,while IL-17 neutralization relieved the inhibition of directional differentiation into astrocytes rather than neurons.In conclusion,serum IL-17 levels were elevated in the early stage of ICH and were negatively correlated with outcome in ICH patients.Animal experiments and cytological investigations therefore demonstrated that IL-17 probably has neurotoxic roles in ICH because of its inhibitory effects on the directional differentiation of NSCs.The application of IL-17 neutralizing antibody may promote the directional differentiation of NSCs into astrocytes.This study was approved by the Clinical Research Ethics Committee of Anhui Medical University of China(For human study:Approval No.20170135)in December 2016.All animal handling and experimentation were reviewed and approved by the Institutional Animal Care and Use Committee of Anhui Medical University(approval No.20180248)in December 2017.
基金Supported by Cultivation Fund of National Natural Science Foundation of China Project(202114)Major Program at School Level(201711).
文摘[Objectives]To explore the expression of interleukin 34(IL-34)in gastric adenocarcinoma tissues and its relationship with apoptosis of gastric adenocarcinoma cells.[Methods]60 cases of surgically resected human gastric adenocarcinoma tissue specimen and 50 cases of adjacent normal gastric mucosa tissue specimen were collected,and the expression of IL-34 protein was determined by immunohistochemical streptavidin-perosidase(SP)method.Cell apoptosis in tissue specimen was detected by TUNEL staining method,and the relationship between IL-34 protein expression and apoptosis of gastric adenocarcinoma cells was analyzed.[Results]Immunohistochemical SP experiment indicated that the expression of IL-34 protein in gastric adenocarcinoma was higher than that in adjacent normal gastric mucosa(P<0.05);its positive expression was related to histological differentiation,TNM stage,invasion depth,and lymph node metastasis of gastric adenocarcinoma(P<0.05),but not to gender and age(P>0.05).TUNEL experiment showed that compared with the adjacent normal gastric mucosa group,the apoptosis index(AI)of gastric adenocarcinoma group was significantly lower(P<0.05);the AI was related to histological differentiation,TNM stage,tumor invasion depth and lymph node metastasis of gastric adenocarcinoma(P<0.05),but not to gender and age(P>0.05).In gastric adenocarcinoma,the AI of IL-34 positive expression group was lower than that of IL-34 negative expression group,and the results were statistically significant(P<0.05).[Conclusions]IL-34 has high expression in gastric adenocarcinoma tissues and is negatively correlated with cancer cell apoptosis.Abnormal expression of IL-34 is involved in the occurrence and development of gastric adenocarcinoma.This provides a new idea for the pathogenesis research and clinical treatment of gastric adenocarcinoma.
