Fichtner-Feigl, Stefan and Fuss, Ivan J. and Young, Cheryl A. and Watanabe, Tomohiro and Geissler, Edward K. and Schlitt, Hans Juergen and Kitani, Atsushi and Strober, Warren (2007) Induction of IL-13 triggers TGF-beta(1)-dependent tissue fibrosis in chronic 2,4,6-trinitrobenzene sulfonic acid colitis. JOURNAL OF IMMUNOLOGY, 178 (9). pp. 5859-5870. ISSN 0022-1767,
Full text not available from this repository. (Request a copy)Abstract
To investigate the immunopathogenesis of inflammation-associated fibrosis, we analyzed the chronic colitis and late-developing fibrosis occurring in BALB/c mice administered weekly doses of intrarectal 2,4,6-trinitrobenzene sulfonic acid. We showed first in this model that an initial Th1 response involving IL-12p70 and IFN-gamma subsides after 3 wk to be supplanted by an IL-23/IL-25 response beginning after 4-5 wk. This evolution is followed by gradually increasing production of IL-17 and cytokines ordinarily seen in a Th2 response, particularly IL-13, which reaches a plateau at 8-9 wk. In vitro stimulation studies suggest that this IL-13 production is dependent on IL-23 and IL-25, but not on IL-12p70. We then show that IL-13 production results in the induction of an IL-13R formerly thought to function only as a decoy receptor, IL-13R alpha(2), and this receptor is critical to the production of TGF-beta(1), and the onset of fibrosis. Thus, if IL-13 signaling through this receptor is blocked by administration of soluble IL-13R alpha(2)-Fc, or by administration of IL-13R alpha 2-specific small interfering RNA, TGF-beta(1) is not produced and fibrosis does not occur. These studies show that in chronic 2,4,6-trinitrobenzene sulfonic acid colitis, fibrosis is dependent on the development of an IL-13 response that acts through a novel cell surface-expressed IL-13R to induce TGF-beta(1). A similar mechanism may obtain in certain forms of human inflammatory bowel disease.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | INFLAMMATORY-BOWEL-DISEASE; NF-KAPPA-B; T-CELLS; TGF-BETA; INTESTINAL INFLAMMATION; CROHNS-DISEASE; CUTTING EDGE; MURINE MODEL; AUTOIMMUNE INFLAMMATION; TGF-BETA-1 PRODUCTION; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Chirurgie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 14 Dec 2020 07:09 |
| Last Modified: | 14 Dec 2020 07:10 |
| URI: | https://pred.uni-regensburg.de/id/eprint/32834 |
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