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Jing Lin, Guiqiu Zhao, Liting Hu, Chengye Che, Nan Jiang, Fungal Keratitis; Potential autocrine regulation of interleukin-33/ST2 signaling of corneal epithelium in Fungal Keratitis. Invest. Ophthalmol. Vis. Sci. 2014;55(13):6276.
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© ARVO (1962-2015); The Authors (2016-present)
Corneal innate immune responses are key mediators of the host’s defense against microbial infection, including fungal keratitis. Interleukin (IL) 33 is well known to promote Th2 type immune responses by signaling through its receptor ST2. However, it is not clear how ST2 responds to IL-33 to induce pro-inflammatory mediator in fungal keratitis. This study was to explore the role of IL-33/ST2 signaling in regulating the pro- inflammatory cytokine production in fungal keratitis and its role in the innate immune response triggered by inactive Af conidia.
In ex vivo donor normal corneal epithelium, IL-33 protein was detected to be located in basal layers and ST2 protein was detected to be located in superficial layers, both of them were stimulated to multiple layers of the epithelium exposed to Af conidia. Af conidia significantly stimulated production of pro- inflammatory cytokines (IL-33, IL-6, IL-1β) by TCECs at both mRNA and protein levels. These stimulated production of pro-inflammatory mediators by Af conidia was blocked by soluble ST2 protein and was stimulated by IL-33. Interestingly, p38 MAPK inhibitor SB203580 also suppressed the production of these pro-inflammatory cytokines induced by Af conidia.
These findings demonstrate that IL-33/ST2 signaling plays an important role in fungal keratitis and it contributes to the innate immune responses triggered by inactive conidia by induction of pro-inflammatory cytokines such as IL-6 and IL-1β through the p38 MAPK pathway, and suggesting a molecular mechanism by which local allergic inflammatory response may be amplified by corneal epithelial cell produced IL-33 through potential autocrine regulation.
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