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PLoS One. 2012;7(9):e45801. doi: 10.1371/journal.pone.0045801. Epub 2012 Sep 20.

Interleukin 27 induces the expression of complement factor H (CFH) in the retina.

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1
Molecular Immunology Section, National Eye Institute, National Institutes of Health, Bethesda, MD, USA.

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.

PMID:
23029250
PMCID:
PMC3447806
DOI:
10.1371/journal.pone.0045801
[Indexed for MEDLINE]
Free PMC Article
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