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

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*

*Corresponding author for this work

Research output: Contribution to journalArticle

26 Scopus citations

Abstract

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 tirst 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.

Original languageEnglish (US)
Pages (from-to)99-105
Number of pages7
JournalInvestigative Ophthalmology and Visual Science
Volume44
Issue number1
DOIs
StatePublished - Jan 1 2003

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

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    Lang, R., Song, P. I., Legat, F. J., Lavker, R. M., Harten, B., Kalden, H., Grady, E. F., Bunnett, N. W., Armstrong, C. A., & Ansel, J. C. (2003). Human corneal epithelial cells express functional PAR-1 and PAR-2. Investigative Ophthalmology and Visual Science, 44(1), 99-105. https://doi.org/10.1167/iovs.02-0357