Effect Of Resveratrol On Expression Of Adhesion Molecules In The Inflammatory Response Of HMESs Induced By Activated Complement Alternative Pathway

Object:To investigate the effect of resveratrol on expression of adhesion molecules during inflammation response and possible mechanisms induced by activated alternative pathway on human microvascular endothelial cells(HMECs) with the use of cobra venom factor(CVF).Method:CVF was used to activate normal human serum,and then the incubated products was used to active HMECs, the concentration of MDA and total SOD activity in the supernatant of cultured HMECs were detected by the method of TBA and WST-8, respectively. Effect of resveratrol with different concentration on oxidative stress level was measured as well. ELISA method was used to detect the expression of P-selectin,ICAM-1,VCAM-1,E-selectin at various time points to determine the effect of complement alternative pathway activation on endothelial cells.Effect of resveratrol, PDTC or AG490 with different concentrations were used to detect their effect on adhesion molecules expression,which were special inhibitors for NF-κB and JAK2 signal pathway,respectively. The phosphorylation of NF-κB p65 subunit under the stimulation of complement alternative pathway activation was detected by Western blot,and intervention of Res,PDTC and AG490 on endothelial cell were assayed as well.Results : The activation of complements alternative pathway could lead to the phosphorylation of NF-κB p65 and up-regulate the expression of P-selectin,ICAM-1,VCAM-1,E-selectin and increase the oxidation levels of endothelial cells. Resveratrol could decrease the concentration of MDA and inhibit the activity of SOD slightly,and reduce the oxidative stress level. Resveratrol and PDTC showed similar inhibition effect on NF-κB p65 phosphorylation,and reduce the expression of ICAM-1 and VCAM-1 of endothelial cells,while exhibit little effect on the expression of P-selectin and E-selectin. AG490 pretreatment could distinctly inhibit the expression of 4 kinds adhesion molecules.Conclusion:Resveratrol could inhibit the adhesion molecules expression induced by activated complement alternative pathway,the mechanism might involve in inhibition on NF-κB pathway activation and increase of oxidation level. JAK2 plays a important role in adhesion molecules expression and may be a more important intervention target in regulating adhesion molecules expression induced by activated complement alternative pathway.