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Gi Sang Yoon, Fu-Shin X. Yu; Tlr5-mediated Upregulation Of Interferon Regulatory Factor 1 (irf1) And C-x-c Motif Chemokine 10 (cxcl10) And Their Role In Corneal Innate Protection. Invest. Ophthalmol. Vis. Sci. 2011;52(14):5817.
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Flagellin pretreatment of the cornea provides protection against Pseudomonas keratitis (PA). Interferon regulatory factor 1 (IRF1) is a transcription factor upregulated by TLR5 activation and is known to be involved in upregulating the microbicidal chemokine, C-X-C motif chemokine 10 (CXCL10). This study was to elucidate the expression of IRF1 and its target gene, CXCL10, in response to flagellin and PA, and their role in corneal epithelial inflammatory response in vitro and in vivo.
Expression of IRF1 in response to flagellin was detected with SuperAarray, RT-PCR and Western blot techniques. siRNA was used to knockdown the expression of IRF1 and consequently, CXCL10. Production and secretion of IP-10 was measured using RT-PCR and/or dot blot. Wild type and IRF1 knockout mice were used to assess the role of IRF1 in cornel protection against PA.
RT-PCR and Western blotting confirmed IRF-1 as one of the transcription factors greatly upregulated in flagellin and bacteria challenged cells. Interestingly, flagellin pretreatment that dampens bacterium-induced cytokine expression also attenuated IRF-1 upregulation. Accordingly knockdown of IRF1 resulted in reduced CXCL10 expression and secretion. However, secreted CXCL10 levels were higher in flagellin-pretreated compared to non-pretreated cells rechallenged with live PA, although CXCL10 RNA levels remained baseline in accordance with dampened IRF1 expression. In vivo, PA infection of flagellin-pretreated IRF1 knockout mice corneas exhibited weakened protection against keratitis compared to flagellin-pretreated WT mice.
IRF1 is a critical transcription factor involved in the corneal response to bacterial infection, including induced production antimicrobial and chemokine CXCL10.
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