title: Interleukin 27 induces the expression of complement factor H (CFH) in the retina.
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.
authors.affiliation: Molecular Immunology Section, National Eye Institute, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Ahjoku
authors.initials: A
authors.lastname: Amadi-Obi
authors.forename: Cheng-Rong
authors.initials: CR
authors.lastname: Yu
authors.forename: Ivy
authors.initials: I
authors.lastname: Dambuza
authors.forename: Sung-Hye
authors.initials: SH
authors.lastname: Kim
authors.forename: Bernadette
authors.initials: B
authors.lastname: Marrero
authors.forename: Charles E
authors.initials: CE
authors.lastname: Egwuagu
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D017242:Complement Factor H / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D006801:Humans; D050856:Interferon Regulatory Factor-1 / Q000235:genetics / Q000378:metabolism; D050835:Interferon Regulatory Factors / Q000235:genetics / Q000378:metabolism; D007378:Interleukins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D008268:Macular Degeneration / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D010211:Papilledema / Q000378:metabolism; D061251:Primary Cell Culture; D012160:Retina / Q000378:metabolism* / Q000473:pathology; D012165:Retinal Ganglion Cells / Q000378:metabolism; D055211:Retinal Photoreceptor Cell Inner Segment / Q000378:metabolism; D031300:Retinal Vasculitis / Q000378:metabolism; D050794:STAT1 Transcription Factor / Q000378:metabolism / Q000502:physiology; D015533:Transcriptional Activation; D014605:Uveitis / Q000378:metabolism; D000099185:Interferon Regulatory Factor-8
chemical_list: D017242:Complement Factor H; D050856:Interferon Regulatory Factor-1; D050835:Interferon Regulatory Factors; D007378:Interleukins; D050794:STAT1 Transcription Factor; D000099185:Interferon Regulatory Factor-8; C486767:Il27 protein, mouse; C494258:Irf1 protein, mouse; C494080:Stat1 protein, mouse