Cholera toxin subunit B inhibits IL-12 and IFN-γ production and signaling in experimental colitis and Crohn's disease. Issue 11 (16th August 2005)

• Record Type: Journal Article
• Authors: Coccia, E M; Remoli, M E; Di Giacinto, C; Del Zotto, B; Giacomini, E; Monteleone, G; Boirivant, M
• Is Part Of: Gut. Volume 54:Issue 11(2005)
• Page Start: 1558
• Page End: 1564
• Publication Date: 2005-08-16
• Subjects: CD, Crohn's disease -- CT, cholera toxin -- IBD, inflammatory bowel disease -- LPMC, lamina propria mononuclear cells -- TNBS, trinitrobenzene sulfonic acid -- UC, ulcerative colitis; Crohn's disease -- cholera toxin B subunit -- interleukin-12 -- interferon-γ -- transcription factors; Gastroenterology -- Periodicals; 616.33
• DOI: 10.1136/gut.2004.062174
• Languages: English
• ISSNs: 0017-5749

Abstract

Abstract : Background and aims: Cholera toxin B subunit (CT-B) is a powerful modulator of immune responses. The authors have previously demonstrated that oral administration of recombinant CT-B (rCT-B) is able to prevent and cure the Crohn's disease (CD)-like trinitrobenzene sulfonic acid (TNBS) mediated colitis. In this study they extended their observations and examined if rCT-B interferes with the molecular signaling underlying the Th1 type response both in TNBS colitis and in ex vivo human CD explants. Methods: TNBS treated mice were fed with rCT-B, and IFN-γ and IL-12 production by colonic lamina propria mononuclear cells (LPMC) was examined by ELISA. In vitro culture of mucosal explants from CD patients and non-inflammatory bowel disease controls, pre-incubated with rCT-B, were examined for IFN-γ and IL-12 production by ELISA and semiquantitative reverse transcription polymerase chain reactions. STAT-1, -4, -6 activation and T-bet expression were examined following rCT-B treatment by western blotting both in TNBS treated mice and in human mucosal explants. Results: rCT-B significantly reduced IL-12 and IFN-γ secretion by LPMC from TNBS treated mice. Consistent with this, rCT-B inhibited both STAT-4 and STAT-1 activation and downregulated T-bet expression. Inhibition of Th1 signaling by CT-B associated with no change in IL-4 synthesis and expression of active STAT-6 indicating that rCT-B does not enhance Th2 cell responses. Moreover, in vitro treatment of CD mucosal explants with rCT-B resulted in reduced secretion of IL-12/IFN-γ and inhibition of STAT-4/STAT-1 activation and T-bet expression. Conclusions: These studies indicate that CT-B inhibits mucosal Th1 cell signaling and suggest that rCT-B may be a promising candidate for CD therapy.