Interleukin-33 expression is specifically enhanced in inflamed mucosa of ulcerative colitis
- 1.4k Downloads
Interleukin (IL)-33 is a cytokine belonging to the IL-1 family. IL-33 has been shown to elicit a Th2-like cytokine response in immune cells. In this study, we investigated IL-33 expression in the inflamed mucosa of patients with inflammatory bowel disease (IBD), and characterized the molecular mechanisms responsible for IL-33 expression in human colonic subepithelial myofibroblasts (SEMFs).
IL-33 mRNA expression was determined by real-time polymerase chain reaction (PCR). IL-33 expression in the IBD mucosa was evaluated by immunohistochemical methods.
IL-33 mRNA expression was significantly elevated in active lesions from patients with ulcerative colitis (UC), but was not detected in inactive lesions from UC patients or in lesions from patients with either active or inactive Crohn’s disease. Colonic SEMFs were identified as a major source of IL-33 in the mucosa. IL-1β and tumor necrosis factor-α (TNF-α) significantly enhanced IL-33 mRNA and protein expression in isolated colonic SEMFs. IL-1β and TNF-α did not affect IL-33 expression in intestinal epithelial cell lines (HT-29 and Caco-2 cells). This IL-1β- and TNF-α-induced IL-33 mRNA expression was mediated by p42/44 mitogen activated protein kinase (MAPK) pathway-dependent activation of nuclear factor (NF)-κB and activator protein (AP)-1.
IL-33, derived from colonic SEMFs, may play an important role in the pathophysiology of UC.
KeywordsIBD Cytokine Biomarker
- 4.Marvie P, Lisbonne M, L’Helgoualc’h A, Rauch M, Turlin B, Preisser L, et al. Interleukin-33 overexpression is associated with liver fibrosis in mice and humans. J Cell Mol Med. 2009 (Epub ahead of print).Google Scholar
- 9.Beltran CJ, Nunez LE, Diaz-Jimenez D, Farfan N, Candia E, Heine C, et al. Characterization of the novel ST2/IL-33 system in patients with inflammatory bowel disease. Inflamm Bowel Dis. 2009 (Epub ahead of print).Google Scholar
- 23.Ding SZ, Olekhnovich IN, Cover TL, Peek RM Jr, Smith MF Jr, Goldberg JB. Helicobacter pylori and mitogen-activated protein kinases mediate activator protein-1 (AP-1) subcomponent protein expression and DNA-binding activity in gastric epithelial cells. FEMS Immunol Med Microbiol. 2008;53:385–94.CrossRefPubMedGoogle Scholar