The novel IL-10 related cytokine IL-26 is increased in active inflammatory bowel disease and intestinal epithelial cells express the functional IL-26 receptor complex

Introduction: Human interleukin-26 (IL-26) signals through a receptor complex consisting of IL-20R1 and IL-10R2. Preliminary studies suggest T lymphocytes as primary source of this cytokine. Aims/Methods: The purpose of this study was to analyze IL-26 receptor expression, signal transduction and specific biological functions of this cytokine system in intestinal epithelial cells (IEC).

Methods: Expression studies were performed by RT-PCR and quantitative PCR. Signal transduction was analyzed by Western blot experiments and ELISA. Cell proliferation was measured by MTS assay and Fas induced apoptosis by flow cytometry. Results: The IEC lines Caco-2, SW480, HCT116 and HT-29 express both IL-26 receptor subunits IL-20R1 and IL-10R2. IL-26 binding to its receptor complex activates ERK-1/2 and SAPK/JNK MAP kinases, and Akt. IL-26 also induced phosphorylation of STAT1 and STAT3. IL-26 slightly decreased cell proliferation while it had no effect on Fas-ligand induced apoptosis. Moreover, IL-26 stimulation increased IL-8 protein expression levels in ELISA assays up to 3.7-fold. IL-26 mRNA expression was increased in inflamed colonic lesions compared to non-inflamed tissue in 8 out of 12 patients with Crohn's disease (CD; average 5.0-fold increase) and in 7 out of 10 patients with ulcerative colitis (UC; average 3.4-fold increase) and correlated highly with the IL-8 expression in these lesions (r=0.659 for CD patients; r=0.788 for UC patients). Conclusion: IEC express the functional IL-26 receptor complex. Binding of IL-26 to its receptor results in phosphorylation of MAP kinases and STAT proteins and an increased expression of proinflammatory cytokines. Moreover, our data indicate a role for this cytokine system in intestinal inflammation as seen in patients with inflammatory bowel disease.