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The Effect of IL-26 on TNF-α-Induced CXCL8 Responses by Colonic Epithelial Cell Lines

ABSTRACT Th17 cells of the intestine and colon can produce several important cytokines during mucosal inflammation. However, few studies have focused on the role of IL-26 in intestinal inflammations. Colonic epithelial cells express receptors for IL-26, and this cytokine has been shown to induce the HT-29 colonic epithelial cell line to produce the chemokine CXCL8. However, epithelial cells would function in a cytokine network environment during mucosal inflammation and any effect of IL-26 on colonic epithelial cell chemokine responses could be affected by the presence of other potent pro-inflammatory cytokines like TNF-α and IL-1. Therefore, we investigated the effect of IL-26 with TNF-α or IL-1 on colonic epithelial cell line secretion of CXCL8. IL-26 alone had no effect on HT-29 or DLD1 cell line CXCL8 secretion. Yet, IL-26 was found to significantly enhance TNF-α-induced, but not IL-1-induced, CXCL8 secretion, but only at high levels of TNF-α. Similar results were seen with DLD1 cells. IL-26 did not enhance TNF-α-induced CXCL8 mRNA levels and did not affect TNF-α-induced IκBα phosphorylation or degradation. However, signaling through ERK and p38 MAPK were determined to be involved in the enhancing effect of IL-26 on the TNF-α-induced CXCL8 secretion, perhaps through known post-translational effects. These results suggest that the role of IL-26 in intestinal inflammation may be limited to enhancing CXCL8 secretion in the presence high levels of TNF-α, such as may occur in inflammatory bowel disease. Abbreviations: DMEM, Dulbecco’s Modified Eagle’s Medium; GAPDH, glyceraldehyde-3-phosphate dehydrogenase; IBD, inflammatory bowel disease; IL, interleukin; ITS, insulin, transferrin, selenium; TBS, Tris buffered saline; TNF, tumor necrosis factor.