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) 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 PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (29) Citing Articles via Google Scholar Google Scholar Articles by Brand, S. Articles by Dambacher, J. Search for Related Content PubMed PubMed Citation Articles by Brand, S. Articles by Dambacher, J.

INFLAMMATION/IMMUNITY/MEDIATORS

IL-22 is increased in active Crohn’s disease and promotes proinflammatory gene expression and intestinal epithelial cell migration

¹Department of Medicine II, University-Hospital Munich-Grosshadern, University of Munich, Munich, Germany; ²Department of Medicine I, St. Josef-Hospital, Ruhr-University, Bochum, Germany; ³Ingenium Pharmaceuticals, Martinsried, Germany; and ⁴Institute of Radiology, University-Hospital Munich-Grosshadern, University of Munich, Munich, Germany

Submitted 1 November 2005 ; accepted in final form 18 November 2005

IL-22 is produced by activated T cells and signals through a receptor complex consisting of IL-22R1 and IL-10R2. The aim of this study was to analyze IL-22 receptor expression, signal transduction, and specific biological functions of this cytokine system in intestinal epithelial cells (IEC). Expression studies were performed by RT-PCR. Signal transduction was analyzed by Western blot experiments, cell proliferation by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium assay and Fas-induced apoptosis by flow cytometry. IEC migration was studied in wounding assays. The IEC lines Caco-2, DLD-1, SW480, HCT116, and HT-29 express both IL-22 receptor subunits IL-22R1 and IL-10R2. Stimulation with TNF-, IL-1, and LPS significantly upregulated IL-22R1 without affecting IL-10R2 mRNA expression. IL-22 binding to its receptor complex activates STAT1/3, Akt, ERK1/2, and SAPK/JNK MAP kinases. IL-22 significantly increased cell proliferation (P = 0.002) and phosphatidylinsitol 3-kinase-dependent IEC cell migration (P < 0.00001) as well as mRNA expression of TNF-, IL-8, and human -defensin-2. IL-22 had no effect on Fas-induced apoptosis. IL-22 mRNA expression was increased in inflamed colonic lesions of patients with Crohn’s disease and correlated highly with the IL-8 expression in these lesions (r = 0.840). Moreover, IL-22 expression was increased in murine dextran sulfate sodium-induced colitis. IEC express functional receptors for IL-22, which increases the expression of proinflammatory cytokines and promotes the innate immune response by increased defensin expression. Moreover, our data indicate intestinal barrier functions for this cytokine-promoting IEC migration, which suggests an important function in intestinal inflammation and wound healing. IL-22 is increased in active Crohn’s disease and promotes proinflammatory gene expression and IEC migration.

interleukin-10-like cytokines; interleukin-22; defensin

This article has been cited by other articles:

				L. Charrier-Hisamuddin, C. L. Laboisse, and D. Merlin ADAM-15: a metalloprotease that mediates inflammation FASEB J, March 1, 2008; 22(3): 641 - 653. [Abstract] [Full Text] [PDF]

				J. Dambacher, F. Beigel, J. Seiderer, D. Haller, B. Goke, C. J Auernhammer, and S. Brand Interleukin 31 mediates MAP kinase and STAT1/3 activation in intestinal epithelial cells and its expression is upregulated in inflammatory bowel disease Gut, September 1, 2007; 56(9): 1257 - 1265. [Abstract] [Full Text] [PDF]

				K. Zitzmann, S. Brand, E. N. De Toni, S. Baehs, B. Goke, J. Meinecke, G. Spottl, H. H.H.D. Meyer, and C. J. Auernhammer SOCS1 Silencing Enhances Antitumor Activity of Type I IFNs by Regulating Apoptosis in Neuroendocrine Tumor Cells Cancer Res., May 15, 2007; 67(10): 5025 - 5032. [Abstract] [Full Text] [PDF]

				G. F. Weber, S. Schlautkotter, S. Kaiser-Moore, F. Altmayr, B. Holzmann, and H. Weighardt Inhibition of Interleukin-22 Attenuates Bacterial Load and Organ Failure during Acute Polymicrobial Sepsis Infect. Immun., April 1, 2007; 75(4): 1690 - 1697. [Abstract] [Full Text] [PDF]

				S. Brand, J. Dambacher, F. Beigel, K. Zitzmann, M. H. J. Heeg, T. S. Weiss, T. Prufer, T. Olszak, C. J. Steib, M. Storr, et al. IL-22-mediated liver cell regeneration is abrogated by SOCS-1/3 overexpression in vitro Am J Physiol Gastrointest Liver Physiol, April 1, 2007; 292(4): G1019 - G1028. [Abstract] [Full Text] [PDF]

				S. M. Sa, P. A. Valdez, J. Wu, K. Jung, F. Zhong, L. Hall, I. Kasman, J. Winer, Z. Modrusan, D. M. Danilenko, et al. The Effects of IL-20 Subfamily Cytokines on Reconstituted Human Epidermis Suggest Potential Roles in Cutaneous Innate Defense and Pathogenic Adaptive Immunity in Psoriasis J. Immunol., February 15, 2007; 178(4): 2229 - 2240. [Abstract] [Full Text] [PDF]