title: IL-33 is induced by amyloid-β stimulation and regulates inflammatory cytokine production in retinal pigment epithelium cells.
abstract: Age-related macular degeneration (AMD) is the predominant cause of irreversible blindness in the elderly population. Despite intensive basic and clinical research, its pathogenesis remains unclear. However, evidence suggests that immunological and inflammatory factors contribute to the pathogenesis of AMD. A newly identified cytokine, IL-33, appears to be an important pro-inflammatory cytokine promoting tissue inflammation. In this study, IL-33 was increased through amyloid-beta(1-40) (Aβ(1-40)) stimulation and regulated inflammatory cytokines including IL-6, IL-8, IL-1β, and TNF-α secretion using different signaling pathways in retinal pigment epithelium (RPE) cells. Furthermore, ST2L, the important component of the IL-33 receptor, was significantly increased following recombinant human IL-33 stimulation in RPE cells. These findings suggest that IL-33-mediated inflammatory responses in RPE cells are involved in the pathogenesis of AMD. Greater understanding of the inflammatory effect of IL-33 and its role in RPE cells should aid the development of future clinical therapeutics and enable novel pharmacological approaches towards the prevention of AMD.
authors: Department of Ophthalmology, Chinese PLA (People's Liberation Army) General Hospital, 28 Fuxing Road, Beijing, 100853, China.
authors: Xiao-Cui
authors: XC
authors: Liu
authors: Xiao-Fei
authors: XF
authors: Liu
authors: Cong-Xiang
authors: CX
authors: Jian
authors: Chen-Jun
authors: CJ
authors: Li
authors: Shou-Zhi
authors: SZ
authors: He
mesh_terms: D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000873:Anthracenes / Q000494:pharmacology; D002070:Butadienes / Q000494:pharmacology; D002460:Cell Line; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D000072179:Interleukin-1 Receptor-Like 1 Protein; D053583:Interleukin-1beta / Q000378:metabolism; D000067596:Interleukin-33; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D007378:Interleukins / Q000096:biosynthesis / Q000378:metabolism*; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008268:Macular Degeneration / Q000276:immunology* / Q000378:metabolism; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors / Q000378:metabolism; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D009570:Nitriles / Q000494:pharmacology; D010446:Peptide Fragments / Q000378:metabolism*; D011725:Pyridines / Q000494:pharmacology; D011956:Receptors, Cell Surface / Q000378:metabolism; D055213:Retinal Pigment Epithelium / Q000276:immunology* / Q000378:metabolism; D013450:Sulfones / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: C434003:3-(4-methylphenylsulfonyl)-2-propenenitrile; D016229:Amyloid beta-Peptides; D000873:Anthracenes; D002070:Butadienes; C079241:IL1RL1 protein, human; C506536:IL33 protein, human; D007093:Imidazoles; D000072179:Interleukin-1 Receptor-Like 1 Protein; D053583:Interleukin-1beta; D000067596:Interleukin-33; D015850:Interleukin-6; D016209:Interleukin-8; D007378:Interleukins; D016328:NF-kappa B; D009570:Nitriles; D010446:Peptide Fragments; D011725:Pyridines; D011956:Receptors, Cell Surface; D013450:Sulfones; D014409:Tumor Necrosis Factor-alpha; C113580:U 0126; C078592:amyloid beta-protein (1-40); C432165:pyrazolanthrone; D048031:JNK Mitogen-Activated Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; C093642:SB 203580