Effect of macrophage migration inhibitory factor on inflammatory cytokines and fibrogenic gene expression in human RPE cells

Proliferative vitreoretinopathy (PVR) is a vision-threatening disease. It is also a common complication resulting from surgery to correct rhegmatogenous retinal detachment. Proliferation and migration of retinal pigment epithelial (RPE) cells and the secretion of extracellular matrix molecules play an important role in the formation of the preretinal membrane in PVR patients. Furthermore, upregulated expression of inflammatory cytokines within the vitreous or subretinal fluid of patients experiencing vitreoretinal disorders may aggravate the inflammatory response and be involved in the development of PVR. PVR is triggered by many inflammatory cytokines and growth factors. Macrophage migration inhibitory factor (MIF), an inflammatory cytokine, is upregulated in the vitreous in PVR patients. However, there is little known concerning the connection between MIF and the expression of inflammatory cytokines, interleukin-6 (IL-6) and monocyte chemotactic-1 (MCP-1), and the fibrogenic gene, collagen I, in human RPE cells. Cell proliferation, migration, and expression of IL-6, MCP-1 and collagen I were assessed using an MTT assay, a Transwell assay, real-time PCR analysis and ELISA kits. Western-blot analysis was used to detect phosphorylation of p38 mitogen activated protein kinase (MAPK) and extracellular signal-regulated kinase (ERK) signaling pathways. The data revealed that MIF promoted the proliferation, migration and expression of IL-6, MCP-1 and collagen I, and phosphorylation of p38 and ERK signaling pathways in RPE cells in vitro. These findings suggest that MIF plays a proinflammatory and profibrotic role in the development of PVR.