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Ahjoku Amadi-Obi, Cheng-Rong Yu, YongJun Lee, Hyun-Mee Oh, Rashid Mahdi, Jenna Burton, Charles Egwuagu; Il-27 Regulates Expression Of Complement Factor H In The Retina Through Signal Transducer And Activator Of Transcription 1 (stat1)-dependent Mechanism. Invest. Ophthalmol. Vis. Sci. 2011;52(14):2286.
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Complement Factor H is an important negative regulator of the alternative complement pathway. It is constitutively expressed in the retina and may play a role in ocular immune privilege by regulating unrestrained complement activation in the eye. Functional defects in the expression of complement factor H gene leading to chronic inflammation and defective clearance of cellular debris by the Retinal Pigment Epithelium, has been implicated in the development of Age-related Macular Degeneration. IL-27 is a heterodimeric IL-12 family cytokine that has anti-inflammatory properties. It is constitutively expressed in the retina and has recently been shown to suppress intraocular inflammation by inhibiting effector CD4 cells that mediate uveitis. In this study we have investigated whether IL-27 contributes to the regulation of complement Factor H expression in the neuroretina.
Primary retinal cells and retinal cell lines were cultured with IL-27 and expression of Complement Factor H mRNA and protein was analyzed by RT-PCR and western blot, respectively. Because IL-27 mediates its biological effects through activation of Signal Transducer and Activator of Transcription 1 (STAT1) and STAT3 pathways we isolated primary retinal cells from wild type, STAT1-deficient and STAT3- deficient retinal cells and examined expression of complement factor H following stimulation with IL-27.
We show that IL-27 induced complement factor H expression in mouse and human retinal cells and it appears to mediate its effect primarily through STAT1 pathway. Interestingly lack of STAT3 in primary retinal cells has minimal effect on the induction of complement factor H by IL-27. In contrast, IL-6 was found to induce complement factor H through STAT3, suggesting that pro- and anti-inflammatory cytokines may regulate complement factor H by differential activation of distinct STAT pathways.
Our data suggest that in addition to suppressing adaptive immune response in the retina, IL-27 may also contribute to the maintenance of ocular Immune privilege by suppressing innate immune responses through up-regulation of complement factor H in the retina. These results further suggest that IL-27 may be useful in the treatment of chronic ocular inflammation.
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