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Peter I. Song, Tonya A. Abraham, Youngmin Park, Adam S. Zivony, Brad Harten, Henry F. Edelhauser, Sherry L. Ward, Cheryl A. Armstrong, John C. Ansel; The Expression of Functional LPS Receptor Proteins CD14 And Toll-Like Receptor 4 in Human Corneal Cells. Invest. Ophthalmol. Vis. Sci. 2001;42(12):2867-2877.
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purpose. Gram-negative bacterial infections of the eye can lead to corneal
bacterial keratitis, visual impairment, and blindness. Many of these
pathologic changes may be mediated by bacterially derived products such
as lipopolysaccharide (LPS). In this investigation, it has been
established for the first time that human corneal cells are capable of
expressing the functional LPS receptor complex proteins, CD14 and
Toll-like receptor 4 (TLR4).
methods. CD14 and TLR4 mRNA expression in human corneal cells was determined by
RT-PCR and Northern blot analysis, and cell surface expression of these
proteins was measured by flow cytometry. LPS-mediated corneal cell
activation was determined by measuring intracellular calcium
mobilization. Cellular cytokine and chemokine secretion in response to
LPS was measured by ELISA. The expression and localization of CD14 in
whole human cornea was determined by immunohistochemistry.
results. Human corneal epithelial, stromal, and endothelial cells expressed CD14
mRNA and cell surface CD14. LPS binding to cornea CD14 resulted in a
rapid intracellular calcium response and the secretion of multiple
proinflammatory cytokines and chemokines. CD14 mRNA expression in
corneal epithelial cells was upregulated by LPS. In addition to CD14,
corneal epithelial cells expressed the functional LPS
receptor–signaling protein TLR4, which was also augmented by LPS.
conclusions. The cornea expresses functional CD14 and TLR4 LPS receptor proteins.
Understanding the function and biology of the corneal LPS receptor
complex may lead to novel therapies for the management of ocular
Gram-negative bacterial infections.
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