Impact of intrarectal chromofungin treatment on dendritic cells-related markers in different immune compartments in colonic inflammatory conditions

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.