u-0126 and Macular-Degeneration

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.

Topics: Amyloid beta-Peptides; Anthracenes; Butadienes; Cell Line; Humans; Imidazoles; Inflammation; Interleukin-1 Receptor-Like 1 Protein; Interleukin-1beta; Interleukin-33; Interleukin-6; Interleukin-8; Interleukins; JNK Mitogen-Activated Protein Kinases; Macular Degeneration; MAP Kinase Signaling System; Mitogen-Activated Protein Kinase 1; Mitogen-Activated Protein Kinase 3; NF-kappa B; Nitriles; Peptide Fragments; Pyridines; Receptors, Cell Surface; Retinal Pigment Epithelium; Sulfones; Tumor Necrosis Factor-alpha