Purchase this article with an account.
Roland Lang, Peter I. Song, Franz J. Legat, Robert M. Lavker, Brad Harten, Henner Kalden, Eileen F. Grady, Nigel W. Bunnett, Cheryl A. Armstrong, John C. Ansel; Human Corneal Epithelial Cells Express Functional PAR-1 and PAR-2. Invest. Ophthalmol. Vis. Sci. 2003;44(1):99-105. doi: 10.1167/iovs.02-0357.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
purpose. The objective of this study was to examine whether HCECs express functional proteinase-activated receptor (PAR)-1 and -2 and evaluate the effects of receptor activation on corneal epithelial cell proinflammatory cytokine production.
methods. Expression of PAR-1 and -2 mRNAs was determined by RT-PCR in cultured primary human corneal epithelial cells (HCECs) and the human corneal epithelial cell line HCE-T. Localization of PAR-1 and -2 in whole normal human corneas was determined by immunofluorescence with PAR-1 and -2 antibodies. The functional competence of PAR-1 and -2 in corneal epithelial cells was assessed by measuring the rapid induction of intracellular [Ca2+] in response to thrombin, trypsin, and specific receptor-activating peptides derived from the tethered ligands of the PAR receptors. HCE-T expression of cytokines (IL-6, IL-8, and TNFα) in response to activation of PAR-1 and -2 was measured by quantitative RT-PCR and ELISA.
results. Functional PAR-1 and -2 were expressed in both HCECs and HCE-T cells. Immunoreactivity for PAR-1 and -2 was detected in the outer epithelial layer of the cornea in whole human corneal sections. Activation of PAR-1 and -2 led to upregulation in HCE-T cells of both expression of mRNA and secretion of the proinflammatory cytokines IL-6, IL-8, and TNFα.
conclusions. The results show for the first time that functional PAR-1 and -2 are present in human cornea. Activation of these receptors results in the production of various corneal epithelial cell proinflammatory cytokines. These observations indicate that PAR-1 and -2 may play an important role in modulating corneal inflammatory and wound-healing responses. These receptors may be useful therapeutic targets in several corneal disease processes.
This PDF is available to Subscribers Only