IL–17 Receptor is Expressed and Functional on Resident Corneal Cells of Both Man and Mouse

Abstract

Abstract: : Purpose: IL–17 is a proinflammatory cytokine associated with a number of inflammatory diseases including herpes stromal keratitis. We investigated whether a receptor for IL–17 was present and functional on cultured human corneal epithelial cells (HCE), human corneal fibroblasts (HCF), and mouse corneal fibroblasts (MCF). Methods: RT–PCR was used to search for IL–17R and IL–17 mRNAs in human and mouse corneal cells. IL–17R protein expression was assessed by immunofluorescence (IF). Supernatants of cultured cells exposed to IL–17 for 24 or 48 hrs were assayed for cytokines by ELISA.Results: Both HCE and HCF expressed IL–17R mRNA and protein as detected by RT–PCR and IF respectively. The receptor was functional as exposure to low dose IL–17 (1–10ng/ml) induced HCF to secrete IL–8 and IL–6 at 43–>200 and 5–11 fold respectively above background. More modest levels of IL–8 and IL–6 (2–3 fold increase) were produced by HCE exposure to IL–17. MCF also expressed IL–17R mRNA and protein, and produced 5–8 fold increases in MIP–2 and 3–4 fold increases in IL–6. Furthermore, both of these proinflammatory mediators were readily detected in murine corneas excised 6 hrs after intracorneal injection of IL–17. Mouse corneal cells exposed to IL–1α were not induced to make IL–17. Conclusions: IL–17R is expressed and functional in HCE, HCF, and MCF as ligand: receptor interaction resulted in IL–8/MIP–2 and IL–6 secretion. These results suggest that in vivo IL–17 may be a facilitator of neutrophil recruitment into the inflamed cornea.

Keywords: cytokines/chemokines • inflammation • cornea: stroma and keratocytes