Research Into The Mechanism Of High Glucose Induce Mesangial Cell Express TNF-α And IL-6

[OBJECTIVE] To investigate the expression of proinflammatory cytokines TNF-αand IL-6 in high glucose,and the effect of p38MAPK specific inhibitor,NF-κB specific inhibitor in glomerular mesangial cells,study the activation of p38MAPK and NF-κB whether or not mediate the expression of TNF-αand IL-6 in high glucose,expecting to elucidate the mechanism of proinflammatory cytokines expression in diabetic nephropathy.[METHODS] 1.Use different glucose density simulating glomerular mesangial cells,detect the expression of phosphorylation p38MAPK by western blotting, NF-κBp65 by cellular immunofluorescence, TNF-α,IL-6 mRNA by RT-PCR,to observe the alteration of phosphorylation p38MAPK,NF-κB,TNF-αand IL-6.2. Prestimulus glomerular mesangial cells in high glucose with p38MAPK specific inhibitor and NF-κB specific inhibitor,detect the expression of phosphorylation p38MAPK,NF-κBp65,TNF-αand IL-6,with the same test method,investigate the alteration of them after refrain the activation of p38MAPK and NF-κB.[RESULTS] 1.The mRNA expression of TNF-αwas up-regulated with glucose concentratioin;when the glucose density between 5.6～20mM, The mRNA expression of IL-6 was up-regulated with glucose concentratioin, but when 25mM,it is lower on the contrary;the expression of phosphorylation p38MAPK was up-regulated with glucose concentratioin;NF-κBp65 expression in nucelus increase and in cytoplasm decrease, with concentration dependent.2.SB203580 restrain the activation of p38MAPK obviously, down-regulate the mRNA expression of TNF-αand IL-6;PDTC restrain the activation of NF-κB obviously, down-regulate the mRNA expression of TNF-αand IL-6;use SB203580 and PDTC together, The mRNA expression of TNF-αand IL-6 descent all the more. [CONCLUSIONS] 1.high glucose up-regulate glomerular mesangial cells expressing TNF-αand IL-6,with concentration dependent,and correlated with the activation of p38MAPK and NF-κB.2.both of the activation of p38MAPK and NF-κB mediate glomerular mesangial cells expressing TNF-αand IL-6 induced by high glucose,and there are across effect.