Role of Protease-Activated Receptors 2 (PAR2) in Ocular Infections and Inflammation

Abstract

Protease-activated receptors (PARs) belong to a unique family of G protein-coupled receptors (GPCRs) that are cleaved at an activation site within the N-terminal exodomain by a variety of proteinases, essentially of the serine (Ser) proteinase family. After cleavage, the new N-terminal sequence functions as a tethered ligand, which binds intramolecularly to activate the receptor and initiate signaling. Cell signals induced through the activation of PARs appear to play a significant role in innate and adoptive immune responses of the cornea, which is constantly exposed to proteinases under physiological or pathophysiological conditions. Activation of PARs interferes with all aspects of the corneal physiology such as barrier function, transports, innate and adoptive immune responses, and functions of corneal nerves. It is not known whether the proteinase released from the microorganism can activate PARs and triggers the inflammatory responses. The role of PAR2 expressed by the corneal epithelial cells and activation by serine protease released from microorganism is discussed here. Recent evidences suggest that activation of PAR2, by the serine proteinases, play an important role in innate and inflammatory responses of the corneal infection.

Proteases and Their Potential Role as Biomarkers and Drug Targets in Dry Eye Disease and Ocular Surface Dysfunction

“…The involvement of PARs in DED was never mentioned until recently when Joossen et al described a significant increase in PAR-2 expression on the corneal tissue of untreated dry eye rats [ 38 ]. Several studies indicate the expression of PAR-1 and PAR-2 in HCE [ 76 , 102 , 103 ]. Lang et al also demonstrated that a specific activation of PAR-2 by trypsin and thrombin increased the production of the proinflammatory cytokines IL-6, IL-8, and TNF-α by HCE [ 102 ].…”