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I. Nishikawa–Ishida, S. Saika, O. Yamanaka, K. Ikeda, Y. Okada, A. Kitano, Y. Ohnishi; Effects Of Mcp–1 On Fibroenic Cytokine Expression In Retinal Pigment Epithelium Cell Line Arpe–19 . Invest. Ophthalmol. Vis. Sci. 2006;47(13):3827.
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© ARVO (1962-2015); The Authors (2016-present)
Transforming growth factor ß (TGFß) plays important/pivotal roles in fibrosis process in proliferative vitreoretinopathy (PVR). It has not been examined if monocyte/macrophage chemoattractant protein–1 (MCP–1) up–regulates fibrogenic cytokines in ARPE–19 cells, while TGFß reportedly up–regulates MCP–1. Here, we examined the effects of MCP–1 on ARPE–19 cells in order to further understand the mechanism of fibrogenic sequelae in PVR. Expression of MCP–1 in PVR tissue was also immunohistochemically examined.
We examined MCP–1 protein expression in the PVR tissues by dual immunostaining with CD68 antibody to detect macrophage distribution. ARPE19 cell culture was treated in the presence or absence of either recombinant MCP–1 and/or TGFß–neutralizing antibody. mRNA expression of MCP–1, TGFß1 and connective tissue growth factor (CTGF) was determined by real–time RT–PCR. Cell migration was examined in wound healing model by scratching monolayer sheet. We finally examined MCP–1and TGFß1 mRNA in a scratch–wounded monolayers of ARPE–19 cells.
MCP–1 protein was detected in a macrophage in human PVR tissues. Adding MCP–1 up–regulated mRNA expression of TGFß1 and CTGF and reduced MCP–1 mRNA expression. Up–regulation of CTGF mRNA by MCP–1 addition was counteracted by further addition of TGFß–neutralization antibody. MCP–1 promoted cell migration in a wound healing model. Producing scratch wound in cell monolayer increased mRNA expression of TGFß1 and MCP–1, and this up–regulation of TGFß1 and MCP–1 were decreased by adding TGFß–neutralizing antibody.
MCP–1 increases CTGF expression through up–regulation of TGFß expression. During cell migration of ARPE–19 up–regulation of TGFß1 results in further expression of MCP–1. TGFß1 and MCP–1 may cooperate progression of PVR.
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