Cholera toxin subunit B inhibits IL-12 and IFN-gamma production and signaling in experimental colitis and Crohn's disease
| Autor: | Monica Boirivant, C. Di Giacinto, M E Remoli, B Del Zotto, Eliana M. Coccia, Giovanni Monteleone, E Giacomini |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2005 |
| Předmět: |
Male
STAT6 protein colitis ex vivo study Inbred Strains animal cell medicine.disease_cause incubation time Western blotting Mice Crohn Disease STAT4 protein mononuclear cell Interferon gamma Intestinal Mucosa Phosphorylation Cells Cultured cholera toxin B subunit gamma interferon interleukin 12 STAT1 protein animal experiment animal model article cell culture controlled study Crohn disease cytokine production cytokine release down regulation enteropathy enzyme activation enzyme linked immunosorbent assay explant in vitro study mouse nonhuman priority journal protein expression quantitative analysis reverse transcription polymerase chain reaction signal transduction Th1 cell Adult Animals Cholera Toxin Colitis DNA-Binding Proteins Humans Immunity Mucosal Interferon Type II Interleukin-12 Mice Inbred Strains Middle Aged Organ Culture Techniques Recombinant Proteins Signal Transduction STAT4 Transcription Factor Th1 Cells Trans-Activators Mucosal Settore MED/12 - Gastroenterologia Cultured Cholera toxin Gastroenterology Interleukin 12 medicine.drug Cell signaling Cells Biology Peripheral blood mononuclear cell Interferon-gamma Immune system medicine Inflammatory Bowel Disease Immunity medicine.disease Molecular biology digestive system diseases Immunology Ex vivo |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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