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 [10.1136/gut.2004.062174].

Cholera toxin subunit B inhibits IL-12 and IFN-gamma production and signaling in experimental colitis and Crohn's disease

MONTELEONE, GIOVANNI;
2005

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-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.
Pubblicato
Rilevanza internazionale
Articolo
Sì, ma tipo non specificato
Settore MED/12 - Gastroenterologia
English
cholera toxin B subunit; gamma interferon; interleukin 12; STAT1 protein; STAT4 protein; STAT6 protein; animal cell; animal experiment; animal model; article; cell culture; colitis; controlled study; Crohn disease; cytokine production; cytokine release; down regulation; enteropathy; enzyme activation; enzyme linked immunosorbent assay; ex vivo study; explant; in vitro study; incubation time; mononuclear cell; mouse; nonhuman; priority journal; protein expression; quantitative analysis; reverse transcription polymerase chain reaction; signal transduction; Th1 cell; Western blotting; Adult; Animals; Cells, Cultured; Cholera Toxin; Colitis; Crohn Disease; DNA-Binding Proteins; Humans; Immunity, Mucosal; Interferon Type II; Interleukin-12; Intestinal Mucosa; Male; Mice; Mice, Inbred Strains; Middle Aged; Organ Culture Techniques; Phosphorylation; Recombinant Proteins; Signal Transduction; STAT4 Transcription Factor; Th1 Cells; Trans-Activators
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 [10.1136/gut.2004.062174].
Coccia, Em; Remoli, Me; Di Giacinto, C; Del Zotto, B; Giacomini, E; Monteleone, G; Boirivant, M
Articolo su rivista
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2108/39200
Citazioni
  • ???jsp.display-item.citation.pmc??? 12
  • Scopus ND
  • ???jsp.display-item.citation.isi??? 22
social impact