HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 285/3/G529    most recent 00050.2003v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (26) Citing Articles via Google Scholar Google Scholar Articles by Bamba, S. Articles by Fujiyama, Y. Search for Related Content PubMed PubMed Citation Articles by Bamba, S. Articles by Fujiyama, Y.

INFLAMMATION/IMMUNITY/MEDIATORS

Regulation of IL-11 expression in intestinal myofibroblasts: role of c-Jun AP-1- and MAPK-dependent pathways

¹Department of Internal Medicine, Shiga University of Medical Science, Seta-Tukinowa, Otsu 520-2192; and ²Department of Pharmacology, Graduate School of Medicine, Osaka City University, Osaka 545-8585, Japan

Submitted 29 January 2003 ; accepted in final form 14 May 2003

IL-11 inhibits the activation of NF-B and induces the Th2 polarization of CD4⁺ T cells. The clinical utility of IL-11 is being investigated in Crohn's disease. However, physiological secretion of IL-11 in the intestine remains unclear. In this study, we investigated IL-11 secretion in human intestinal subepithelial myofibroblasts (SEMFs). Intestinal SEMFs were isolated from the human colonic mucosa. IL-11 secretion and mRNA expression were determined by ELISA and Northern blot analysis. The activating protein (AP)-1-DNA binding activity was evaluated by EMSA. IL-11 secretion was induced by IL-1 and transforming growth factor (TGF)-1. These were also observed at the mRNA level. The EMSAs demonstrated that both IL-1 and TGF-1 induced AP-1 activation within 2 h after stimulation, and a blockade of AP-1 activation by the recombinant adenovirus containing a dominant negative c-Jun markedly reduced the IL-1- and TGF-1-induced IL-11 mRNA expression. IL-1 and TGF-1 induced an activation of ERK p42/44 and p38 MAP kinases, and the MAP kinase inhibitors (SB-202190, PD-98059, and U-0216) significantly reduced the IL-1- and TGF-1-induced IL-11 secretion. The upregulation of IL-11 mRNA by IL-1- and TGF-1 was also mediated by a p38 MAP kinase-mediated mRNA stabilization. The combination of IL-1 and TGF-1 additively enhanced IL-11 secretion. Intestinal SEMFs secreted IL-11 in response to IL-1- and TGF-1. Mucosal IL-11 secretion might be important as an anti-inflammatory response in the pathogenesis of intestinal inflammation.

interleukin-11; inflammatory bowel diseases; transforming growth factor-1; interleukin-1

This article has been cited by other articles:

				W.-H. Kan, J.-T. Hsu, Z.-F. Ba, M. G. Schwacha, J. Chen, M. A. Choudhry, K. I. Bland, and I. H. Chaudry p38 MAPK-dependent eNOS upregulation is critical for 17{beta}-estradiol-mediated cardioprotection following trauma-hemorrhage Am J Physiol Heart Circ Physiol, June 1, 2008; 294(6): H2627 - H2636. [Abstract] [Full Text] [PDF]

				K. M. Naugler, K. A. Baer, and M. J. Ropeleski Interleukin-11 antagonizes Fas ligand-mediated apoptosis in IEC-18 intestinal epithelial crypt cells: role of MEK and Akt-dependent signaling Am J Physiol Gastrointest Liver Physiol, March 1, 2008; 294(3): G728 - G737. [Abstract] [Full Text] [PDF]

				B. Hoang, A. Trinh, and R. A. Edwards Decreased MAPK- and PGE2-dependent IL-11 production in Gi{alpha}2-/- colonic myofibroblasts Am J Physiol Gastrointest Liver Physiol, June 1, 2007; 292(6): G1511 - G1519. [Abstract] [Full Text] [PDF]

				Y. Kang, W. He, S. Tulley, G. P. Gupta, I. Serganova, C.-R. Chen, K. Manova-Todorova, R. Blasberg, W. L. Gerald, and J. Massague Breast cancer bone metastasis mediated by the Smad tumor suppressor pathway PNAS, September 27, 2005; 102(39): 13909 - 13914. [Abstract] [Full Text] [PDF]