IL-33 Signaling Protects from Murine Oxazolone Colitis by Supporting Intestinal Epithelial Function. Issue 12 (December 2015)

• Record Type: Journal Article
• Authors: Waddell, Amanda; Vallance, Jefferson E.; Moore, Preston D.; Hummel, Amy T.; Wu, David; Shanmukhappa, Shiva K.; Fei, Lin; Washington, M. Kay; Minar, Phillip; Coburn, Lori A.; Nakae, Susumu; Wilson, Keith T.; Denson, Lee A.; Hogan, Simon P.; Rosen, Michael J.
• Is Part Of: Inflammatory bowel diseases. Volume 21:Issue 12(2015:Dec.)
• Publication Date: 2015-12
• Subjects: ulcerative colitis -- inflammatory bowel disease -- interleukin-33 -- epithelial cells -- oxazolone; Inflammatory bowel diseases -- Periodicals; Colitis, Ulcerative -- Periodicals; Crohn Disease -- Periodicals; Inflammatory Bowel Diseases -- Periodicals; 616.344
• DOI: 10.1097/MIB.0000000000000532
• Languages: English
• ISSNs: 1078-0998

Abstract

Abstract : Background: IL-33, a member of the IL-1 cytokine family that signals through ST2, is upregulated in ulcerative colitis (UC); however, the role of IL-33 in colitis remains unclear. IL-33 augments type 2 immune responses, which have been implicated in UC pathogenesis. We sought to determine the role of IL-33 signaling in oxazolone (OXA) colitis, a type 2 cytokine-mediated murine model of UC. Methods: Colon mucosal IL-33 expression was compared between pediatric and adult UC and non-IBD patients using immunohistochemistry and real-time PCR. OXA colitis was induced in WT, IL-33 −/−, and ST2 −/− mice, and histopathology, cytokine levels, and goblet cells were assessed. Transepithelial resistance was measured across IL-33-treated T84 cell monolayers. Results: Colon mucosal IL-33 was increased in pediatric patients with active UC and in OXA colitis. IL-33 −/− and ST2 −/− OXA mice exhibited increased disease severity compared with WT OXA mice. OXA induced a mixed mucosal cytokine response, but few differences were observed between OXA WT and IL-33 −/− or ST2 −/− mice. Goblet cells were significantly decreased in IL-33 −/− and ST2 −/− OXA compared with WT OXA mice. IL-33 augmented transepithelial resistance in T84 cells, and this effect was blocked by the ERK1/2 inhibitor PD98, 059. Conclusions: OXA colitis is exacerbated in IL-33 −/− and ST2 −/− mice. Increased mucosal IL-33 in human UC and murine colitis may be a homeostatic response to limit inflammation, potentially through effects on epithelial barrier function. Further investigation of IL-33 protective mechanisms would inform the development of novel therapeutic approaches. Abstract : Article first published online 6 August 2015.Supplemental Digital Content is Available in the Text.