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Maria-Jesus Benito, Carmen Garcia-Vazquez, Michael E. Stern, Margarita Calonge, Amalia Enriquez-De-Salamanca; In Vitro Study Of The Involvement Of IL-17 In Chronic And Severe Ocular Surface Inflammatory Processes. Invest. Ophthalmol. Vis. Sci. 2012;53(14):2323.
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IL-17 has been reported to play an important role in the pathogenesis of chronic inflammatory ocular surface diseases; however, little is known about the role of IL-17 in the regulation of cytokine/chemokine secretion by ocular surface epithelial cells. The aim of this study was to evaluate the role of IL-17 in cytokine/chemokine secretion and in the expression of receptors involved in inflammatory processes in ocular surface epithelial cells.
Corneal (HCE) and conjunctival (IOBA-NHC) epithelial cells were stimulated with IL-17 (20 ng/ml), TNF-α (25 ng/ml), and IL-17+TNF-α for 48h in serum-free culture medium. Cell supernatants were collected for cytokine/chemokine (18 plex) and TGF-β isoforms (3 plex) determination by inmmunobead-based assays in a Luminex-IS 100. TGF-β receptor (RI, RII and RIII) expression was determined in basal and stimulated cells by Western blot and immunofluorescence assays.
A significant upregulation of IL-6 (HCE and IOBA-NHC), IL-8 (HCE) and fractalkine (IOBA-NHC) secretion was observed after 48h stimulation with IL-17. IL-17 synergistically enhanced TNF-α stimulated production of IL-6 and IL-8 by IOBA-NHC cells, and significantly downregulated TNF-α-stimulated production of IP-10 and RANTES by HCE cells. IL-17 increased the secretion of TGF-β2 active form by HCE cells, while in combination with TNF-α it decreased TGF-β1 latent form compared to IL-17 alone stimulation. IL-17 significantly increased TGF-β-RI expression in both cell lines, while in combination with TNF-α it downregulated TGF-β-RI,-RII and -RIII expression in IOBA-NHC cells, and TGF-β-RI and RII in HCE cells.
IL-17 may play an important role amplifying the inflammatory response through the release of proinflammatory mediators by corneal and conjunctival epithelial cells. Also, IL-17 seems to play a differential regulatory role in cytokine/chemokine production and TGF-β receptors expression stimulated with TNF-α depending on the cell type.
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