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L. Liu, E. A. Walker, P. M. Stewart, I. Khan, S. J. Curnow, P. I. Murray, G. R. Wallace, S. Rauz; The Immunological Roles of Toll-Like Receptors and Glucocorticoids in Corneal Cells. Invest. Ophthalmol. Vis. Sci. 2009;50(13):5546.
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Toll like receptors (TLRs) are a family of pattern recognition molecules that act as first line of defence against a variety of pathogens upon the recognition of pathogen-associated microbial patterns (PAMPs) Glucocorticoids are widely used in the treatment of ocular infections. Cell specific glucocorticoid (cortisol) production via the enzyme 11-beta hydroxysteroid dehydrogenase type 1 (11β-HSD1) may contribute to the immune privileged status of the ocular surface, either alone, or in combination with the production of antimicrobial peptides (AMPs), via the TLR pathway. In this study, human corneal keratocytes were characterised for the presence and function of TLR and glucocorticoid pathways.
Primary human corneal epithelial cells and keratocytes were cultured from corneal scleral tissue surplus to surgical requirement after approval from the local ethics committee. RT-PCR was carried out for the presence of TLR1-10, 11β-HSD1, GR, and H6PDH. Both corneal epithelial cells and keratocytes were challenged with TLR agonists 1-9 for 16 h and the production of IL-8 were examined by ELISA. In addition, 29 other inflammatory cytokines, chemokines and grow factors were examined by Luminex bead assay. Specific 11β-HSD1 enzyme activity assays were also carried out on corneal epithelial cells and keratocytes at basal levels, and following stimulation with TLR agonists.
Both human corneal epithelial cells and keratocytes express mRNAs for 11β-HSD1, GR, H6PDH and all TLRs except TLR6 and TLR8. Stimulation of these cells with the TLR agonists induced proinflammatory cytokine and chemokine production. Treatment with TLR3 agonist in particular stimulated a large range of chemokine production on corneal epithelial cells. The keratocytes demonstrated higher levels of 11β-HSD1 activity than corneal epithelial cells and the activity was not altered by treatment with TLR agonists.
Human corneal epithelial cells and keratocytes have the potential to respond to microbial pathogens through TLR-mediated pathways, resulting in the production of cytokines and chemokines. They are also capable of intracellular production of glucocorticoids via the enzyme 11β-HSD1, which may have a profound impact on the ocular immune response.
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