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S.X. Zhang, J.J. Wang, A. Dashti, T.J. Lyons, J.–X. Ma; Pigment Epithelium–Derived Factor (PEDF) Suppresses Oxidized Ldl–Induced Monocyte Chemoattractant Protein–1 Production via Anti–Oxidation Activity . Invest. Ophthalmol. Vis. Sci. 2006;47(13):1833.
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© ARVO (1962-2015); The Authors (2016-present)
Pigmented epithelial–derived factor (PEDF) is a neurotrophic factor and an angiogenesis inhibitor. Recently we have shown that PEDF is an endogenous anti–inflammatory factor in the eye. However, the mechanisms underlying the PEDF activity on anti–inflammation are still unclear. In the present study, we have investigated the effect of PEDF on cytokine production in human pericyte induced by heavily oxidized glycated LDL (HOG–LDL), and further explored the mechanisms of PEDF activity on anti–oxidation.
Cultured primary human pericytes were exposed to HOG–LDL or native LDL (N–LDL) at 100 µg/ml with or without PEDF at different concentrations of 10, 40, and 160 nM for 3, 12, and 24 h. The reactive oxygen species (ROS) production in the cells was determined using the fluorescent probe carboxy–H2DCFDA. The monocyte chemoattractant protein–1 (MCP–1) secreted in the medium was measured by ELISA.
At 3 h and 24 h after treatment with HOG–LDL, the intracellular ROS generation was significantly elevated when compared with control cells, as well as N–LDL–exposed cells. MCP–1 secretion was significantly increased after exposure of the cells to HOG–LDL for 24 h. PEDF at 10, 40 and 160 nM showed a dose–dependent inhibition of MCP–1 expression induced by HOG–LDL, suggesting an anti–inflammatory effect of PEDF in pericytes. PEDF at 160 nM completely blocked ROS generation induced by HOG–LDL, suggesting that the anti–inflammatory effect of PEDF in pericytes may be at least partially through its anti–oxidation activity.
PEDF inhibits HOG–LDL–induced ROS generation and subsequent MCP–1 production in pericyte. The anti–oxidation activity of PEDF may be partially responsible for its anti–inflammatory function.
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