Induction of interleukin-8 gene expression and protein secretion by C-reactive protein in ARPE-19 cells

C-reactive protein (CRP) is an acute phase reactant and its level rises rapidly during inflammation. Recent studies have suggested the potential involvement of CRP in the pathogenesis of age-related macular degeneration (AMD). To delineate the functional roles of CRP in inflammatory response by the ocular posterior segments, the effects of CRP on ARPE-19, an immortalized human retinal pigment epithelia (hRPE) cell line, were investigated in the present study. Treatment of ARPE-19 cells with CRP resulted in enhanced NF-kB nuclear translocation and dose-dependent transient induction of IL-8 mRNA synthesis and protein secretion. Stimulated expression of VEGF, but not MCP-1 by CRP was also observed. The induced IL-8 expression was transient and peaked at 12 h post stimulation. In the presence of inhibitors for NF-kB, p38, MEK and JNK, the CRP-induced IL-8 production was abolished by 99.5 ± 2.3, 97.8 ± 2.1, 55.3 ± 2.5 and 37.3 ± 1.3%, respectively. Neutralization of Fc gamma receptors by anti-CD32 and CD64 antibodies produced 39.9 ± 1.6 and 59.5 ± 2.6% reduction, respectively, of CRP-stimulated IL-8 secretion, whereas that by anti-CD16 antibody had no effect. This study suggests that the pro-inflammatory effects of CRP in ARPE-19 cells may contribute to the inflammatory retinal diseases by induction of pro-inflammatory cytokines such as IL-8. This induction is mediated by NF-kB and multiple MAPK pathways through Fc gamma receptors.