Kiessling, Stephan and Mueller-Newen, Gerhard and Leeb, Sandra N. and Hausmann, Martin and Rath, Heiko C. and Strater, Jorn and Spottl, Tanja and Schlottmann, Klaus and Grossmann, Johannes and Montero-Julian, F. A. and Schoelmerich, Juergen and Andus, Tilo and Buschauer, Armin and Heinrich, Peter C. and Rogler, Gerhard (2004) Functional expression of the interleukin-11 receptor alpha-chain and evidence of antiapoptotic effects in human colonic epithelial cells. JOURNAL OF BIOLOGICAL CHEMISTRY, 279 (11). pp. 10304-10315. ISSN 0021-9258, 1083-351X
Full text not available from this repository. (Request a copy)Abstract
A tissue-protective effect of interleukin-11 (IL-11) for the intestinal mucosa has been postulated from animal models of inflammatory bowel disease (IBD). Despite the fact that the clinical usefulness of the anti-inflammatory effects of this cytokine is presently investigated in patients with IBD, there are no data available regarding the target cells of IL-11 action and the mechanisms of tissue protection within the human colonic mucosa. IL-11 responsiveness is restricted to cells that express the interleukin-11 receptor alpha-chain (IL-11Ralpha) and an additional signal-transducing subunit (gp130). In this study, we identified the target cells for IL-11 within the human colon with a new IL-11Ralpha monoclonal antibody and investigated the functional expression of the receptor and downstream effects of IL-11-induced signaling. Immunohistochemistry revealed expression of the IL-11Ralpha selectively on colonic epithelial cells. HT-29 and colonic epithelial cells (CEC) constitutively expressed IL-11Ralpha mRNA and protein. Co-expression of the signal-transducing subunit gp130 was also demonstrated. IL-11 induced signaling through triggering activation of the Jak-STAT pathway without inducing antiinflammatory or proliferative effects in colonic epithelial cells. However, IL-11 stimulation resulted in a dose-dependent tyrosine phosphorylation of Akt, a decreased activation of caspase-9, and a reduced induction of apoptosis in cultured CEC. In HLA-B27 transgenic rats treated with IL-11, a reduction of apoptotic cell numbers was found. This study demonstrates functional expression of the IL-11Ralpha restricted on CEC within the human colonic mucosa. IL-11 induced signaling through triggering activation of the Jak-STAT pathway, without inducing anti-inflammatory or proliferative effects. The beneficial effects of IL-11 therapy are likely to be mediated by CEC via activation of the Akt-survival pathway, mediating antiapoptotic effects to support mucosal integrity.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | RECOMBINANT HUMAN INTERLEUKIN-11; SIGNAL TRANSDUCER GP130; SMALL-INTESTINAL-MUCOSA; ACTIVE CROHNS-DISEASE; FACTOR-KAPPA-B; GROWTH-FACTOR; MOLECULAR-CLONING; TYROSINE PHOSPHORYLATION; HEMATOPOIETIC CYTOKINE; ENDOTHELIAL-CELLS; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine 600 Technology > 615 Pharmacy |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin I Chemistry and Pharmacy > Institute of Pharmacy > Alumni or Retired Professors > Pharmaceutical/Medicinal Chemistry II (Prof. Buschauer) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 21 Jul 2021 10:41 |
| Last Modified: | 21 Jul 2021 10:41 |
| URI: | https://pred.uni-regensburg.de/id/eprint/37880 |
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