Protease–Activated Receptor–4 Induction of Human Corneal Epithelial Cytokines

Abstract

Abstract: : Purpose: Protease–activated receptors (PARs) are a novel family of G–protein linked receptors that are capable of modulating a wide range of biological activities including inflammation, wound healing, and tissue repair. The role of PARs in mediating corneal inflammatory responses needs to be defined. In this study we assessed the role of PAR–4 in mediating inflammatory cytokine production in human corneal epithelial cells. Methods: The expression of PAR–4 in HCE–T human corneal epithelial cells was determined by real time RT–PCR and immunohistochemistry. PAR–4 function was assessed by measuring intracellular Ca++ responses to a specific PAR–4 receptor agonist. HCE–T inflammatory cytokine production was determined by real time RT–PCR and ELISA. Results: Our studies indicated that human corneal epithelial cells expressed functional PAR–4. PAR–4 activation by a specific receptor agonist resulted in augmented IL–1–alpha, IL–1–beta, IL–6, and IL–8 proinflammatory cytokines. PAR–4 activation in HCE–T cells had no effect on TNF–alpha production. Conclusions: The results of these studies indicate for the first time that human corneal epithelial cells express functional PAR–4. Activation of corneal epithelial PAR–4 results in the production of the pro–inflammatory cytokines IL–1–alpha, IL–1–beta, IL–6 and IL–8. These results further support the role of PARs in mediating corneal inflammatory responses.

Keywords: inflammation • cornea: epithelium • cornea: basic science