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.
Highlights
Protease-activated receptors (PARs) belong to a distinctive family of the seven transmembrane G protein-coupled receptors (GPCRs) that are cleaved at an activation site within the N-terminal exodomain by the serine (Ser) proteinase family [1,2,3,4,5]
We have shown that PAR1 and PAR2 transcripts were constitutively expressed in human corneal epithelial (HCE) cells and Acanthamoeba plasminogen activator (aPA) induced up regulation of PAR2, but not PAR1 transcript in the HCE cells
The potential role of PAR2 antagonist in attenuating proinflammatory cytokine IL-8 induced by Acanthamoeba plasminogen activator, aPA, in human corneal epithelial (HCE) cells, is summarized in figure 6
Summary
Protease-activated receptors (PARs) belong to a distinctive family of the seven transmembrane G protein-coupled receptors (GPCRs) that are cleaved at an activation site within the N-terminal exodomain by the serine (Ser) proteinase (or serine endopeptidases) family [1,2,3,4,5]. Lang et al [7] first time demonstrated the PAR1 and PAR2 expression and their functional activity in proinflammatory cytokines secretion in human corneal epithelial (HCE) cells. We have demonstrated that Acanthamoeba castellanii trophozoites’ secreted serine protease, Acanthamoeba plasminogen activator (aPA) [8], induces proinflammatory cytokine IL-8 by the activation of PAR2 signaling in HCE cells [9].
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