Background Activation of signal transducer and activator of transcription 6 (STAT6) plays a critical role in the late phase of Th2-dependent allergy induction. STAT6 is essential to Th2 cell differentiation, recruit...Background Activation of signal transducer and activator of transcription 6 (STAT6) plays a critical role in the late phase of Th2-dependent allergy induction. STAT6 is essential to Th2 cell differentiation, recruitment, and effector function. Our previous study confirmed that DNA vaccination inhibited STAT6 expression of spleen cells induced by allergen. In the present study, we determined whether DNA vaccine encoding Dermatophagoides pteronyssinus group 2 (Der p2 ) could down-regulate the expression and activation of STAT6 in lung tissue from asthmatic mice. Methods After DNA vaccine immunization, BALB/c mice were sensitized by intmperitoneal injection and challenged by intranasal instillation of rDer p2. The levels of the cytokines IL-4 and IL-13 in BAL fluid were measured by enzyme-linked immunosorbent assay. The lung tissue was assessed by immunohistochemical staining with anti-STAT6. The protein expression of STAT6 was determined by Western blot. The activation of STAT6 binding ability was analyzed with electrophoretic mobility shift assay. Results DNA vaccine encoding Der p2 allergen effectively decreased the levels of IL-4 and IL-13 in the asthmatic mice. Histological evidence and Western blot showed that the expression of STAT6 in the DNA treated mice was markedly attenuated. STAT6 binding to specific DNA motif in lung tissue from the gene vaccinated mice was inhibited. Condusion DNA vaccine encoding Der p2 prevents allergic pulmonary inflammation probably by inhibiting the STAT6 signaling pathway in mice with Der p2 allergen-induced allergic airway infammafion.展开更多
The effects of compound Sophorae Flavescen-tis Jiechangrong capsule(CSFJC)on the expression of nuclear factor-κB p65(NF-κB p65)and signal transducer and activator of transcription 6(STAT6)in the intestinal mucosa of...The effects of compound Sophorae Flavescen-tis Jiechangrong capsule(CSFJC)on the expression of nuclear factor-κB p65(NF-κB p65)and signal transducer and activator of transcription 6(STAT6)in the intestinal mucosa of patients with ulcerative colitis and the possible mechanism were investigated.Eighteen patients with ulcerative colitis were randomly divided into a traditional Chinese medicine(TCM)group(n=11)treated by CSFJC and a western medicine(WM)group(n=7)treated by Sulfasalazine tablets.The treatment duration lasted eight weeks.Before and after the treatment,the symptoms and the physical signs were observed,and the routine stool test,the colonoscopy,and pathological examination were performed in the two groups.The expression levels of NF-κB p65 and STAT6 were detected by using immuno-histochemistry.The results showed that the total effective rate of the curative effectiveness in TCM and WM groups was 100%and 71.4%,respectively,and the total effective rate of colonic mucosa lesion in TCM and WM groups was 90.9%and 71.4%,respectively,with the differences being significant(all P<0.05).The total effective rate of syndromes of damp-heat blocking according to the TCM in TCM and WM groups was 90.9%and 71.4%,respectively.After the treatment,the expression of NF-κB p65 and STAT6 in the two groups was decreased,and the decrease of NF-κB p65 and STAT6 expression in TCM group was more significant than in WM group(P<0.05).It was concluded that CSFJC can inhibit the activation and expression of NF-κB p65 and STAT6 in the intestinal mucosa of patients with ulcerative colitis,which is a possible mechanism for CSFJC treating ulcerative colitis.展开更多
The expression of signal transducer and activator of transcription 6(STAT6)and nuclear factor-κB(NF-κB)in the colonic mucosa of patients with ulcerative colitis(UC)was examined.Real-time polymer-ase chain reaction a...The expression of signal transducer and activator of transcription 6(STAT6)and nuclear factor-κB(NF-κB)in the colonic mucosa of patients with ulcerative colitis(UC)was examined.Real-time polymer-ase chain reaction and immunohistochemistry were used to detect the expression of STAT6 and NF-κB p65 at both mRNA and protein levels in the colonic mucosa of patients with UC and healthy volunteers.The results showed that the expression levels of STAT6 and NFκB p65 in the colonic mucosa of patients with UC were significantly higher than in normal controls at both mRNA and protein levels.These data suggest that STAT6 and NFκB p65 perhaps play an important role in the pathogenesis of UC and underscore the potential value of anti-UC strategies in the clinical management of this disease.展开更多
基金The study was supported by grants from the National 863 High Technology Research and Development Program, China (No.2002AA214011) and the National Natural Science Foundation of China (No.30260101,30271226).
文摘Background Activation of signal transducer and activator of transcription 6 (STAT6) plays a critical role in the late phase of Th2-dependent allergy induction. STAT6 is essential to Th2 cell differentiation, recruitment, and effector function. Our previous study confirmed that DNA vaccination inhibited STAT6 expression of spleen cells induced by allergen. In the present study, we determined whether DNA vaccine encoding Dermatophagoides pteronyssinus group 2 (Der p2 ) could down-regulate the expression and activation of STAT6 in lung tissue from asthmatic mice. Methods After DNA vaccine immunization, BALB/c mice were sensitized by intmperitoneal injection and challenged by intranasal instillation of rDer p2. The levels of the cytokines IL-4 and IL-13 in BAL fluid were measured by enzyme-linked immunosorbent assay. The lung tissue was assessed by immunohistochemical staining with anti-STAT6. The protein expression of STAT6 was determined by Western blot. The activation of STAT6 binding ability was analyzed with electrophoretic mobility shift assay. Results DNA vaccine encoding Der p2 allergen effectively decreased the levels of IL-4 and IL-13 in the asthmatic mice. Histological evidence and Western blot showed that the expression of STAT6 in the DNA treated mice was markedly attenuated. STAT6 binding to specific DNA motif in lung tissue from the gene vaccinated mice was inhibited. Condusion DNA vaccine encoding Der p2 prevents allergic pulmonary inflammation probably by inhibiting the STAT6 signaling pathway in mice with Der p2 allergen-induced allergic airway infammafion.
基金supported by grants from the Postdoctoral Science Foundation of China(No.2005037679)the National Natural Science Foundation of China(Grant No.30772878).
文摘The effects of compound Sophorae Flavescen-tis Jiechangrong capsule(CSFJC)on the expression of nuclear factor-κB p65(NF-κB p65)and signal transducer and activator of transcription 6(STAT6)in the intestinal mucosa of patients with ulcerative colitis and the possible mechanism were investigated.Eighteen patients with ulcerative colitis were randomly divided into a traditional Chinese medicine(TCM)group(n=11)treated by CSFJC and a western medicine(WM)group(n=7)treated by Sulfasalazine tablets.The treatment duration lasted eight weeks.Before and after the treatment,the symptoms and the physical signs were observed,and the routine stool test,the colonoscopy,and pathological examination were performed in the two groups.The expression levels of NF-κB p65 and STAT6 were detected by using immuno-histochemistry.The results showed that the total effective rate of the curative effectiveness in TCM and WM groups was 100%and 71.4%,respectively,and the total effective rate of colonic mucosa lesion in TCM and WM groups was 90.9%and 71.4%,respectively,with the differences being significant(all P<0.05).The total effective rate of syndromes of damp-heat blocking according to the TCM in TCM and WM groups was 90.9%and 71.4%,respectively.After the treatment,the expression of NF-κB p65 and STAT6 in the two groups was decreased,and the decrease of NF-κB p65 and STAT6 expression in TCM group was more significant than in WM group(P<0.05).It was concluded that CSFJC can inhibit the activation and expression of NF-κB p65 and STAT6 in the intestinal mucosa of patients with ulcerative colitis,which is a possible mechanism for CSFJC treating ulcerative colitis.
文摘The expression of signal transducer and activator of transcription 6(STAT6)and nuclear factor-κB(NF-κB)in the colonic mucosa of patients with ulcerative colitis(UC)was examined.Real-time polymer-ase chain reaction and immunohistochemistry were used to detect the expression of STAT6 and NF-κB p65 at both mRNA and protein levels in the colonic mucosa of patients with UC and healthy volunteers.The results showed that the expression levels of STAT6 and NFκB p65 in the colonic mucosa of patients with UC were significantly higher than in normal controls at both mRNA and protein levels.These data suggest that STAT6 and NFκB p65 perhaps play an important role in the pathogenesis of UC and underscore the potential value of anti-UC strategies in the clinical management of this disease.