Inflammatory cytokine secretion and toll-like receptor 4 activation in retinal pigment epithelium induced by oxidized low-density lipoprotein

Native and oxidized (OX) low-density lipoprotein (LDL) may contribute to the pathogenesis of age-related macular degeneration (AMD). In this study, we investigated the effects of lipoproteins, including n-LDL and OX-LDL, on the expression of inflammation factors, interleukin-6 (IL-6) and interleukin-1β (IL-1β), in vivo and in cultured retinal pigment epithelial (RPE) cells. The potential role of Toll-like receptor 4 (TLR4) was preliminarily explored. Fifteen male Sprague-Dawley rats were randomized into three groups and injected intravenously with PBS, low n-LDL (1 mg/kg), and high n-LDL (4 mg/kg) for 14 days. Immunohistochemistry analysis of retina sections was conducted to detect IL-6 and IL-1β. ARPE-19 cells were incubated with 10-100 mg/mL n-LDL or OX-LDL for 24 h. Reverse transcription polymerase chain reaction was used to detect IL-6, IL-1β and TLR4 mRNA levels in ARPE-19. IL-6 and IL-1β protein expression was measured by enzyme-linked immune sorbent assay. Activation of TLR4 and extracellular signal-regulated kinase (ERK) protein were evaluated by western blot analysis. One-way analysis of variance was used to compare differences. As a result, circulating LDL increased both IL-6 and IL-1β expression in rat retina tissue. OX-LDL treatment increased IL-6 and IL-1β expression in ARPE-19 cells, and activated TLR4-ERK signaling pathway. In conclusion, LDL activates inflammation cytokines in rat retina. OX-LDL induces inflammation promotion and TLR4-ERK signaling pathway upregulation in cultured RPE cells.