Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Lang, R; Song, PI; Legat, FJ; Lavker, RM; Harten, B; Kalden, H; Grady, EF; Bunnett, NW; Armstrong, CA; Ansel, JC.
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
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- Co-Autor*innen der Med Uni Graz
- Legat Franz
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- Abstract:
- 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. 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 [Ca(2+)] 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 TNFalpha) in response to activation of PAR-1 and -2 was measured by quantitative RT-PCR and ELISA. 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 TNFalpha. 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.
- Find related publications in this database (using NLM MeSH Indexing)
- Base Sequence -
- Calcium - metabolism
- Cell Line -
- Cornea - metabolism
- Cytokines - biosynthesis
- DNA Primers - chemistry
- Enzyme-Linked Immunosorbent Assay -
- Epithelial Cells - metabolism
- Fluorescent Antibody Technique, Indirect -
- Humans -
- Molecular Sequence Data -
- RNA, Messenger - metabolism
- Receptor, PAR-1 -
- Receptor, PAR-2 -
- Receptors, Thrombin - genetics
- Receptors, Thrombin - metabolism
- Reverse Transcriptase Polymerase Chain Reaction -
- Thrombin - pharmacology
- Trypsin - pharmacology
- Up-Regulation -