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 12h 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.
Wang
Yu
Y
Department of Ophthalmology, People's Hospital of Peking University, Beijing 100044, China.
Bian
Zong-Mei
ZM
Yu
Wen-Zhen
WZ
Yan
Zheng
Z
Chen
Wei-Chih
WC
Li
Xiao-Xin
XX
D002097:C-Reactive Protein / Q000494:pharmacology*; D002460:Cell Line; D018932:Chemokine CCL2 / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004591:Electrophoresis, Polyacrylamide Gel; D004797:Enzyme-Linked Immunosorbent Assay; D015870:Gene Expression; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics* / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D016328:NF-kappa B / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis / Q000378:metabolism; D055213:Retinal Pigment Epithelium / Q000187:drug effects* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
C111835:CCL2 protein, human; D018932:Chemokine CCL2; D016209:Interleukin-8; D016328:NF-kappa B; D012333:RNA, Messenger; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D002097:C-Reactive Protein