The exact causes of inflammatory bowel disease(IBD)are not yet fully defined.From a vast body of literature,we know that the immune response has long been involved in the pathogenesis of IBD,including both ulcerative ...The exact causes of inflammatory bowel disease(IBD)are not yet fully defined.From a vast body of literature,we know that the immune response has long been involved in the pathogenesis of IBD,including both ulcerative colitis and Crohn’s disease.A variety of specific alterations can lead to immune activation and inflammation directed to the colon,as revealed by some animal models.Current research has focused on the role of antibodies in downstream events and mechanisms of autoimmunity and inflammation.It is not well known whether the production of antibodies is a serologic consequence of IBD,or if it is a result of barrier dysfunction induced by inflammation.Here,we present a new hypothesis to distinguish the complex links between genetic susceptibility,barrier dysfunction,commensal and pathologic microbial factors and inflammatory response(especially autoantibodies)in the pathogenesis of IBD.To ascertain the hypothesis,we developed a pilot model with the concept of the presence of antibodies against enteric bacterial antigens in IBD.Results confirmed our hypothesis.Our hypothesis suggests the possibility of subcutaneous vaccination of animals with administration of all or specific enteric bacterial antigens.展开更多
AIM:To investigate whether miRNA-155(miR-155)dysregulates apical junctional complex(AJC)protein expression in experimental severe acute pancreatitis(SAP).METHODS:Twenty-four male BALB/c mice were randomly assigned to ...AIM:To investigate whether miRNA-155(miR-155)dysregulates apical junctional complex(AJC)protein expression in experimental severe acute pancreatitis(SAP).METHODS:Twenty-four male BALB/c mice were randomly assigned to two groups:the SAP group(n=12)receiving sequential intraperitoneal injection of 50μg/kg caerulein and 10 mg/kg lipopolysaccharide over 6h,and the control group(n=12)receiving intraperitoneal injection of normal saline.Animals were sacrificed3 h following the last injection for collection of blood samples and pancreas and distal ileal segment specimens.Routine pancreas and intestine histology was used to assess SAP pathology and intestinal epithelial barrier damage.Levels of serum amylase,diamine oxidase(DAO),and tumor necrosis factor(TNF)-αwere determined using commercial kits.Total RNA samples were isolated from intestinal epithelial specimens and reversely transcribed into cDNA.miR-155 and RhoA mRNA expression profiles were determined using quantitative real-time polymerase chain reaction.Target genes for miR-155 were predicted using the miRTarBase database,RNA22 and PicTar computational methods.Western blotting was performed to quantitate the protein expression levels of the target gene RhoA,as well as zonula occludens(ZO)-1 and E-cadherin,two AJC component proteins.RESULTS:Intraperitoneal injection of caerulein and lipopolysaccharide successfully induced experimental acute pancreatic damage(SAP vs control,10.0±2.0vs 3.2±1.2,P<0.01)and intestinal epithelial barrier damage(3.2±0.7 vs 1.4±0.7,P<0.01).Levels of serum amylase(21.6±5.1 U/mL vs 14.3±4.2 U/mL,P<0.01),DAO(21.4±4.1 mg/mL vs 2.6±0.8 mg/mL,P<0.01),and TNF-α(61.0±15.1 ng/mL vs 42.9±13.9 ng/mL,P<0.01)increased significantly in SAP mice compared to those in control mice.miR-155 was significantly overexpressed in SAP intestinal epithelia(1.94±0.50 fold vs 1.03±0.23 fold,P<0.01),and RhoA gene containing three miR-155-specific binding sites in the three prime untranslated regions was one of the target genes for miR-155.RhoA(22.7±5.展开更多
文摘The exact causes of inflammatory bowel disease(IBD)are not yet fully defined.From a vast body of literature,we know that the immune response has long been involved in the pathogenesis of IBD,including both ulcerative colitis and Crohn’s disease.A variety of specific alterations can lead to immune activation and inflammation directed to the colon,as revealed by some animal models.Current research has focused on the role of antibodies in downstream events and mechanisms of autoimmunity and inflammation.It is not well known whether the production of antibodies is a serologic consequence of IBD,or if it is a result of barrier dysfunction induced by inflammation.Here,we present a new hypothesis to distinguish the complex links between genetic susceptibility,barrier dysfunction,commensal and pathologic microbial factors and inflammatory response(especially autoantibodies)in the pathogenesis of IBD.To ascertain the hypothesis,we developed a pilot model with the concept of the presence of antibodies against enteric bacterial antigens in IBD.Results confirmed our hypothesis.Our hypothesis suggests the possibility of subcutaneous vaccination of animals with administration of all or specific enteric bacterial antigens.
基金Supported by The research grants from Shanghai Municipal Science and Technology CommissionNo.114119b2900+1 种基金Shanghai Municipal Key Laboratory of Pancreatic DiseaseNo.P2012006
文摘AIM:To investigate whether miRNA-155(miR-155)dysregulates apical junctional complex(AJC)protein expression in experimental severe acute pancreatitis(SAP).METHODS:Twenty-four male BALB/c mice were randomly assigned to two groups:the SAP group(n=12)receiving sequential intraperitoneal injection of 50μg/kg caerulein and 10 mg/kg lipopolysaccharide over 6h,and the control group(n=12)receiving intraperitoneal injection of normal saline.Animals were sacrificed3 h following the last injection for collection of blood samples and pancreas and distal ileal segment specimens.Routine pancreas and intestine histology was used to assess SAP pathology and intestinal epithelial barrier damage.Levels of serum amylase,diamine oxidase(DAO),and tumor necrosis factor(TNF)-αwere determined using commercial kits.Total RNA samples were isolated from intestinal epithelial specimens and reversely transcribed into cDNA.miR-155 and RhoA mRNA expression profiles were determined using quantitative real-time polymerase chain reaction.Target genes for miR-155 were predicted using the miRTarBase database,RNA22 and PicTar computational methods.Western blotting was performed to quantitate the protein expression levels of the target gene RhoA,as well as zonula occludens(ZO)-1 and E-cadherin,two AJC component proteins.RESULTS:Intraperitoneal injection of caerulein and lipopolysaccharide successfully induced experimental acute pancreatic damage(SAP vs control,10.0±2.0vs 3.2±1.2,P<0.01)and intestinal epithelial barrier damage(3.2±0.7 vs 1.4±0.7,P<0.01).Levels of serum amylase(21.6±5.1 U/mL vs 14.3±4.2 U/mL,P<0.01),DAO(21.4±4.1 mg/mL vs 2.6±0.8 mg/mL,P<0.01),and TNF-α(61.0±15.1 ng/mL vs 42.9±13.9 ng/mL,P<0.01)increased significantly in SAP mice compared to those in control mice.miR-155 was significantly overexpressed in SAP intestinal epithelia(1.94±0.50 fold vs 1.03±0.23 fold,P<0.01),and RhoA gene containing three miR-155-specific binding sites in the three prime untranslated regions was one of the target genes for miR-155.RhoA(22.7±5.
