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Deprecated: Implicit conversion from float 229.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 J+Ocul+Pharmacol+Ther 2015 ; 31 (7): 419-28 Nephropedia Template TP
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Inflammatory Cytokine-Mediated Regulation of Thrombospondin-1 and CD36 in Conjunctival Cells #MMPMID26154920
J Ocul Pharmacol Ther 2015[Sep]; 31 (7): 419-28 PMID26154920show ga
Purpose: Increased expression of transforming growth factor-?2 (TGF-?2) is reported in the conjunctiva of dry eye patients with no increase of anti-inflammatory activity of TGF-?2. Our aim was to compare the expression of molecules involved in TGF-?2 activation, thrombospondin-1 (TSP-1) and CD36, during murine and human conjunctival inflammation.Methods: Human conjunctival tissue from cadaveric donors, human conjunctival epithelial primary cells and fibroblasts, and murine conjunctivas were immunostained for TSP-1, CD36, or TGF-?2. Inflamed conjunctival tissues were obtained from C57BL/6 wild-type (WT) mice induced to develop experimental dry eye (EDE) with 10 days of desiccating conditions and scopolamine injections and TSP-1-deficient (TSP1?/?) mice, which spontaneously develop Sjögren's syndrome-associated conjunctival inflammation with age. Immunostaining intensities were compared using ImageJ software. Cultures of human conjunctival fibroblasts were stimulated with IL-1? and both secreted protein and message levels of TSP-1, CD36, and TGF-?2 were analyzed.Results: TSP-1 and CD36 were detectable in human and murine conjunctival tissues as well as primary conjunctival epithelial cells and fibroblasts. Increased conjunctival immunostaining of TGF-?2 and reduced CD36 were detected in EDE mice compared with WT mice. Interestingly, increased TGF-?2 and CD36 conjunctival immunostaining was detected in TSP1?/? mice. The expression of TSP-1 and CD36 was downregulated in IL-1?-stimulated conjunctival fibroblasts at both the protein and message level, while active TGF-?2 was undetected.Conclusions: The absence or reduced expression of either of the molecules involved in TGF-?2 activation supports proinflammatory conditions in the conjunctiva. Changes in TSP-1 and CD36 may serve as potential biomarkers of conjunctival inflammation.