BACKGROUND Chromofungin(CHR:chromogranin-A 47-66)is a chromogranin-A derived peptide with anti-inflammatory and anti-microbial properties.Ulcerative colitis(UC)is characterized by a colonic decrease of CHR and a dysre...BACKGROUND Chromofungin(CHR:chromogranin-A 47-66)is a chromogranin-A derived peptide with anti-inflammatory and anti-microbial properties.Ulcerative colitis(UC)is characterized by a colonic decrease of CHR and a dysregulation of dendritic CD11c+cells.AIM To investigate the association between CHR treatment and dendritic cells(DCs)-related markers in different immune compartments in colitis.METHODS A model of acute UC-like colitis using dextran sulphate sodium(DSS)was used in addition to biopsies collected from UC patients.RESULTS Intrarectal CHR treatment reduced the severity of DSS-induced colitis and was associated with a significant decrease in the expression of CD11c,CD40,CD80,CD86 and interleukin(IL)-12p40 in the inflamed colonic mucosa and CD11c,CD80,CD86 IL-6 and IL-12p40 within the mesenteric lymph nodes and the spleen.Furthermore,CHR treatment decreased CD80 and CD86 expression markers of splenic CD11c+cells and decreased NF-κB expression in the colon and of splenic CD11c+cells.In vitro,CHR decreased CD40,CD80,CD86 IL-6 and IL-12p40 expression in naïve bone marrow-derived CD11c+DCs stimulated with lipopolysaccharide.Pharmacological studies demonstrated an impact of CHR on the NF-κB pathway.In patients with active UC,CHR level was reduced and showed a negative linear relationship with CD11c and CD86.CONCLUSION CHR has protective properties against intestinal inflammation via the regulation of DC-related markers and CD11c+cells.CHR could be a potential therapy of UC.展开更多
基金Crohn's and Colitis Canada,No.P46601Canadian Foundation for Innovation,No.P39902+2 种基金Children's Hospital Research Institute of Manitoba,No.P45040Natural Sciences and Engineering Research Council,No.P41224and Manitoba Health Research Council,No.P41118(to Ghia JE).
文摘BACKGROUND Chromofungin(CHR:chromogranin-A 47-66)is a chromogranin-A derived peptide with anti-inflammatory and anti-microbial properties.Ulcerative colitis(UC)is characterized by a colonic decrease of CHR and a dysregulation of dendritic CD11c+cells.AIM To investigate the association between CHR treatment and dendritic cells(DCs)-related markers in different immune compartments in colitis.METHODS A model of acute UC-like colitis using dextran sulphate sodium(DSS)was used in addition to biopsies collected from UC patients.RESULTS Intrarectal CHR treatment reduced the severity of DSS-induced colitis and was associated with a significant decrease in the expression of CD11c,CD40,CD80,CD86 and interleukin(IL)-12p40 in the inflamed colonic mucosa and CD11c,CD80,CD86 IL-6 and IL-12p40 within the mesenteric lymph nodes and the spleen.Furthermore,CHR treatment decreased CD80 and CD86 expression markers of splenic CD11c+cells and decreased NF-κB expression in the colon and of splenic CD11c+cells.In vitro,CHR decreased CD40,CD80,CD86 IL-6 and IL-12p40 expression in naïve bone marrow-derived CD11c+DCs stimulated with lipopolysaccharide.Pharmacological studies demonstrated an impact of CHR on the NF-κB pathway.In patients with active UC,CHR level was reduced and showed a negative linear relationship with CD11c and CD86.CONCLUSION CHR has protective properties against intestinal inflammation via the regulation of DC-related markers and CD11c+cells.CHR could be a potential therapy of UC.
