Human corneal epithelial cells express functional PAR-1 and PAR-2

Area of Science:

• Ophthalmology
• Cell Biology
• Immunology

Background:

• Proteinase-activated receptors (PARs) are G protein-coupled receptors involved in various physiological processes.
• PAR-1 and PAR-2 have been implicated in inflammatory responses in different tissues.
• The role of PAR-1 and PAR-2 in human corneal epithelial cells (HCECs) remains largely unexplored.

Purpose of the Study:

• To investigate the expression and function of PAR-1 and PAR-2 in HCECs.
• To determine the effect of PAR-1 and PAR-2 activation on proinflammatory cytokine production in HCECs.

Main Methods:

• RT-PCR was used to assess mRNA expression of PAR-1 and PAR-2 in HCECs and HCE-T cells.
• Immunofluorescence staining localized PAR-1 and PAR-2 in human corneal sections.
• Functional assays measured intracellular calcium ([Ca(2+)]) flux upon receptor activation.
• Quantitative RT-PCR and ELISA quantified cytokine (IL-6, IL-8, TNF-alpha) expression and secretion.

Main Results:

• Functional PAR-1 and PAR-2 were expressed in both primary HCECs and the HCE-T cell line.
• PAR-1 and PAR-2 immunoreactivity was observed in the outer epithelial layer of normal human corneas.
• Activation of PAR-1 and PAR-2 in HCE-T cells significantly upregulated the expression and secretion of IL-6, IL-8, and TNF-alpha.

Conclusions:

• This study provides the first evidence of functional PAR-1 and PAR-2 in the human cornea.
• Activation of these receptors induces the production of proinflammatory cytokines by corneal epithelial cells.
• PAR-1 and PAR-2 represent potential therapeutic targets for corneal inflammatory diseases and wound healing.