Effect Of PEDF On The Expression Of MCP-1、IL-6in Cultured Human Renal Mesangial Cells

Obiective: To observe the impact of pigment epithelium-derived factor (PEDF) to theexpression of monocyte chemoattractant Protein-1(MCP-1) andinterleukin-6(IL-6) in glomerular mesangial cells. And discuss the possiblemechanism.Methods: Renal mesangial cells were incubated with medium containing differentconcentration of glucose (10、20、30mmol/L) in vitro for differenttimes(12h、24h、48h), detect the expression of MCP-1、IL-6mRNA byReactive-transcription porlymerase chain reaction (RT-PCR); mesangialcells were treated with different concentration of PEDF(10、40、160nmol/L),The levels of cytokines including MCP-1、IL-6in cultured medium weremeasured by enzyme-linked immunosorbent assay (ELISA) and the mRNAwere detected by RT-PCR, to observe the impact of PEDF to those twoinflammatory factors; to detect the expression of NF-κB p65byimmunofluorescence assay.Results:(1) Mesangial cells incubated with medium of5.6mmol/L concentration ofglucose can express a basic level of MCP-1、IL-6. Those two inflammatorywere up-regulated under high glucose condition with concentrationdependent and peaked under the concentration of20mmol/L. When it addsto30mmol/L, the expression of MCP-1didn`t increase anymore, while theIL-6decreased(P<0.05). Both of then were up-regulated with timedependent.(2) the high-glucose induced up-regulation of MCP-1and IL-6were largely blocked by PEDF with concentration dependent. When it addsto160nmol/L, PEDF almost completely blocked the up-regulation of MCP-1、IL-6induced by high glucose.(3) The signal of NF-κB wastranslocated from the cytoplasm to the nuclei after incubated with highglucose, PEDF largely blocked the nuclear translocation of NF-κB.Conclusions:(1) high glucose condition up-regulated the expression of MCP-1、IL-6mRNA in mesangial cells, may contribute to the development andprogression of diabetic nephropathy.(2) PEDF suppressed the expression ofMCP-1、IL-6mRNA and protein in high glucose medium, suggested thatPEDF against diabetic nephropathy may be partially through itsanti-inflammatory effect.(3) PEDF inhibits the nuclear translocation ofNF-κB in mesangial cells in a high-glucose medium. suggest that therenoprotective effect of PEDF may be partially through the NF-κB pathway.