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

• Published in: Immunological investigations Vol. 48; no. 8; pp. 822 - 834
• Main Authors: Weishaar, Isabelle M., Young, Rebecca S., Wiles, Brody M., McGee, Dennis W.
• Format: Journal Article
• Language: English
• Published: England Taylor & Francis 17.11.2019
• Subjects: Cell Line, Tumor; Cells, Cultured; Colon - cytology; Colon - drug effects; Colon - metabolism; CXCL8; epithelial; Epithelial Cells - drug effects; Epithelial Cells - metabolism; ERK; HT29 Cells; Humans; IL-26; Interleukin-1 - pharmacology; Interleukin-8 - genetics; Interleukin-8 - metabolism; Interleukins - pharmacology; MAP Kinase Signaling System - drug effects; NF-KappaB Inhibitor alpha - metabolism; p38 MAPK; p38 Mitogen-Activated Protein Kinases - metabolism; Phosphorylation - drug effects; TNF; Tumor Necrosis Factor-alpha - pharmacology; IL-26; epithelial; CXCL8; TNF; p38 MAPK; ERK
• ISSN: 0882-0139; 1532-4311
• DOI: 10.1080/08820139.2019.1594247

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.