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-gamma 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-gamma 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-gamma 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-gamma 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.
Coccia E.M., R.M. (2005). Cholera toxin subunit B inhibits IL-12 and IFN-gamma production and signaling in experimental colitis and Crohn's disease. GUT, 54(11), 1558-1564.
|Tipologia:||Articolo su rivista|
|Citazione:||Coccia E.M., R.M. (2005). Cholera toxin subunit B inhibits IL-12 and IFN-gamma production and signaling in experimental colitis and Crohn's disease. GUT, 54(11), 1558-1564.|
|Settore Scientifico Disciplinare:||Settore MED/12 - Gastroenterologia|
|Revisione (peer review):||Sì, ma tipo non specificato|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1136/gut.2004.062174|
|Stato di pubblicazione:||Pubblicato|
|Data di pubblicazione:||2005|
|Titolo:||Cholera toxin subunit B inhibits IL-12 and IFN-gamma production and signaling in experimental colitis and Crohn's disease|
|Autori:||Coccia E.M., Remoli M.E., Di Giacinto C., Del Zotto B., Giacomini E., Monteleone G., Boirivant M.|
|Appare nelle tipologie:||01 - Articolo su rivista|