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

American Journal of Physiology - Gastrointestinal and Liver Physiology - Tập 290 Số 4 - Trang G827-G838 - 2006
Stephan Brand1, Florian Beigel, Torsten Olszak, Kathrin Zitzmann, Sören T. Eichhorst, Jan‐Michel Otte, Helmut Diepolder, Andreas Marquardt, Wolfgang Jagla, Andreas Popp, Stéphane Leclair, Karin A. Herrmann, Julia Seiderer, Thomas Ochsenkühn, Burkhard Göke, Christoph J. Auernhammer, Julia Dambacher
1Department of Medicine II, University-Hospital Munich-Grosshadern, University of Munich, Germany. [email protected]

Tóm tắt

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-α, IL-1β, 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-α, IL-8, and human β-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.

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American Journal of Physiology - Gastrointestinal and Liver Physiology

Tập 290 Số 4

G827-G838

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