interleukin-8 and Retinitis

The ubiquitin-proteasome pathway (UPP) plays an important role in regulating gene expression. Retinal pigment epithelial cells (RPE) are a major source of ocular inflammatory cytokines. In this work we determined the relationship between impairment of the UPP and expression of inflammation-related factors. The UPP could be impaired by oxidative stress or chemical inhibition. Impairment of the UPP in RPE increased the expression of several inflammatory cytokines, such as IL-6 and IL-8. However, the expression of monocyte chemoattractant protein-1 (MCP-1) and complement factor H (CFH) and was reduced upon impairment of the UPP. These data suggest that impairment of the UPP in RPE may be one of the causes of retinal inflammation and abnormal functions of monocyte and the complement system during the pathogenesis of age-related macular degeneration.

Topics: Cell Line; Chemokine CCL2; Complement Factor H; Humans; Interleukin-6; Interleukin-8; Macular Degeneration; Oxidative Stress; Proteasome Endopeptidase Complex; Retinal Pigment Epithelium; Retinitis; Ubiquitin

Chronic inflammation is implicated in the pathogenesis of AMD. The source of chronic inflammation is often attributed to the progressive activation of immune cells over time. However, recent studies have shown that senescent cells can alter tissue microenvironment via secretion of growth factors, proteases, and inflammatory cytokines and might be an additional source of chronic inflammation. We hypothesized that altered secretory pattern in Aβ-induced senescent RPE cells may contribute to compromised RPE barrier integrity and chronic inflammation in AMD.. Senescence was assessed by measuring the SA-β-Galactosidase activity, the expressions of p16(INK4a) and ATM, and cell cycle analysis. Expressions of IL-8 and MMPs were analyzed by RT-PCR, ELISA, and gelatin zymography. The barrier structures of RPE cells were detected by actin-tracker, ZO-1, claudin-19, occludin immunochemistry, and Western blot; barrier function was analyzed by measuring transepithelial resistance (TER) and transepithelial diffusion rate of FITC-dextran. For inhibitory studies, MMP-9 was inhibited by RNA interference strategy.. Aβ promotes RPE cells to enter senescence and secrete higher concentrations of IL-8 and MMP-9. Secretion of MMP-9 is associated with compromised barrier integrity and with processing of IL-8 to a more activated form. Silence of MMP-9 preserved the barrier integrity of senescent RPE cells.. The altered secretory phenotype of senescent RPE cells may contribute to age-related inflammation in AMD. Chinese Abstract.

Topics: Amyloid beta-Peptides; Cellular Microenvironment; Cellular Senescence; Chronic Disease; Epithelial Cells; Fetus; Humans; Interleukin-8; Macular Degeneration; Matrix Metalloproteinase 9; Occludin; Peptide Fragments; Retinal Pigment Epithelium; Retinitis; RNA, Small Interfering; Zonula Occludens-1 Protein