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Overaccumulation of all\u2010<jats:italic>trans<\/jats:italic>\u2010retinal (atRAL) has been proposed as the pathogenic factor in both diseases. By incubating retinal pigment epithelium (RPE) cells with atRAL, we showed that C5b\u20109 membrane attack complexes (MACs) were generated mainly through complement alternative pathway. An increase in complement factor B (CFB) expression as well as downregulation of complement regulatory proteins CD46, CD55, CD59, and CFH were observed in RPE cells after atRAL treatment. Furthermore, interleukin\u20101\u03b2 production was provoked in both atRAL\u2010treated RPE cells and microglia\/macrophages. Coincubation of RPE cells with interleukin\u20101 receptor antagonist (IL1Ra) and atRAL ameliorated complement activation and downregulated CFB expression by attenuating both p38 and c\u2010Jun N\u2010terminal kinase (JNK) signaling pathways. Our findings demonstrate that atRAL induces an autocrine\/paracrine IL\u20101\/IL\u20101R signaling to promote complement alternative pathway activation in RPE cells and provide a novel perspective on the pathomechanism of macular degeneration.<\/jats:p>","DOI":"10.1002\/jcp.30103","type":"journal-article","created":{"date-parts":[[2020,10,9]],"date-time":"2020-10-09T12:06:28Z","timestamp":1602245188000},"page":"3660-3674","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["IL\u20101\/IL\u20101R signaling induced by all\u2010<i>trans<\/i>\u2010retinal contributes to complement alternative pathway activation in retinal pigment epithelium"],"prefix":"10.1002","volume":"236","author":[{"given":"Xinxuan","family":"Cheng","sequence":"first","affiliation":[{"name":"Fujian Provincial Key Laboratory of Ophthalmology and Visual Science School of Medicine, Eye Institute of Xiamen University, Xiamen University  Xiamen 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