Whole blood mRNA expression levels of immunoregulatory EBI3 and T helper 1 cell-associated IFNG, HLX1 and IL12A correlate with relapse risk in natalizumab-treated multiple sclerosis
MULTIPLE SCLEROSIS JOURNAL
Authors: Petersen, E. R.; Sondergaard, H. Bach; Oturai, A.; Jensen, P. E. H.; Sorensen, P. S.; Sellebjerg, F.; Bornsen, L.
Abstract
Interleukin 27 Induces the Expression of Complement Factor H (CFH) in the Retina
PLOS ONE
Authors: Amadi-Obi, Ahjoku; Yu, Cheng-Rong; Dambuza, Ivy; Kim, Sung-Hye; Marrero, Bernadette; Egwuagu, Charles E.
Abstract
Complement factor H (CFH) is a central regulator of the complement system and has been implicated in the etiology of age-related macular degeneration (AMD), a leading cause of blindness in the elderly. In view of previous studies showing that reduced expression of CFH in the retina is a risk factor for developing AMD, there is significant interest in understanding how CFH expression is regulated in the retina. In this study, we have shown that the anti-inflammatory cytokine, IL-27, induced CFH expression in mouse retinal cells and human retinal pigmented epithelial cells (RPE) through STAT1-mediated up-regulation of Interferon Regulatory Factor-1 (IRF-1) and IRF-8. We further show that cells in the ganglion and inner-nuclear layers of the retina constitutively express IRF-1 and IRF-8 and enhanced CFH expression in the retina during ocular inflammation correlated with significant increase in the expression of IRF-1, IRF-8 and IL-27 (IL-27p28 and Ebi3). Our data thus reveal a novel role of IL-27 in regulating complement activation through up-regulation of CFH and suggest that defects in IL-27 signaling or expression may contribute to the reduction of CFH expression in the retina of patients with AMD.
COA
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