The Expression Of MCP-1in Systemic Lupus Erythematosus And Its Regulation Of TWEAK,Fn14,TTGF-β1,IL-6in Human Renal Mesangial Cells

Objective:1To determine the plasma levels of monocyte chemoattractant protein1in systemic lupus erythematosus patients and evaluate its correlation withlupus nephritis.2To investigate the regulation of TWEAK, Fn14, TGF-β1, IL-6invitro human renal mesangial cells(HRMCs) induced by monocytechemotactant protein1(MCP-1)and its possible mechanism in lupus nephritispathogenesis.Method:1The plasma levels of MCP-1were measured by enzyme linkedimmunosorbent assay in54SLE patients (including40SLE patients withlupus nephritis,14SLE patients with non-lupus nephritis) and22healthycontrols, and its correlation with SLEDAI and nephritis-associated laboratorytests were analyzed.2Vtrio human renal mesangial cells were induced by medium containingdifferent concentrations of MCP-1（5ng/ml,25ng/ml,50ng/ml,100ng/ml）for72h and100ng/ml MCP-1for different time(24h,48h,72h); real-timefluorescence quantitative polymerase chain reaction were used to detectTWEAK,Fn14,TGF-β1, IL-6mRNA expression. Vtrio human renalmesangial cells in climbing pieces were treated by100ng/ml MCP-1for72h， the protein expression of TWEAK, Fn14, TGF-β1, IL-6were measured byimmunohistochemistry.Result:1The plasma levels of MCP-1were significantly elevated in SLEpatients than in healthy controls (P<0.01); the plasma MCP-1levels in LNwere also significantly higher than these in healthy controls (P<0.01); thesignificant association between the plasma MCP-1levels and SLEDAI wereobserved in SLE patients(r=0.381, P<0.01) and LN patients(r=0.408,P<0.01);in LN patients,the plasma MCP-1levels were positively correlated withproteinuria (r=0.563, P<0.001), the number of urinary white cell (r=0.251,P<0.05) and urinary N-acetyl-b-D-glucosaminidasis (r=0.587, P<0.001).2Real-time fluorescence quantitative polymerase chain reaction resultswere shown: different concentrations of MCP-1mediate HRMCs72h byupregulating gene expression of TWEAK,Fn14,TGF-β1,IL-6with theincrease of concentration in a certain range. Significant differences wereobserved between the MCP-1treatment groups and control groups (allP<0.05); Fn14mRNA between5ng/ml MCP-1groups and control groups hadno statistically significant differences (P>0.05). Different concentrations ofMCP-1compared between two groups had statistically significant differences(all P<0.05);100ng/ml MCP-1mediate HRMCs different times byupregulating gene expression of TWEAK,Fn14,TGF-β1,IL-6with theincrease of time in a certain range;significant differences were observedbetween the MCP-1treatment groups and control groups(0h)(allP<0.05);different time of MCP-1compared with each groups had statisticallysignificant differences(all P<0.05). 3Immunohistochemistry analysis showed: Tweak,Fn14,TGF-β1,IL-6values of average IOD in experimental groups were higher than those in thecontrol groups and significant differences were observed(all P<0.01).Conclusion:1The plasma levels of MCP-1in SLE patients were significantlyincreased and correlated with disease activity and renal involvement, andMCP-1can be used as assessment of LN activity.2MCP-1can promote the gene expression of TWEAK, Fn14, TGF-β1,IL-6in HRMCs by dose and time dependent manners in a certain range ofconcentration and time.3MCP-1can increase the protein expression of TWEAK, Fn14,TGF-β1, IL-6in HRMCs.4MCP-1may upregulate the expression of TWEAK, Fn14, TGF-β1,IL-6in HRMCs and participate in the pathological process of LN.