Sublytic C5b-9 induces IL-6 and TGF-β1 production by glomerular mesangial cells in rat Thy-1 nephritis through p300-mediated C/EBPβ acetylation

CCAAT/enhancer-binding protein (C/EBP)-enhanced IL-6 and TGF-1 promoter activity and p300-mediated C/EBP acetylation were involved in up-regulation of IL-6 and TGF-1 expression in GMCs attacked by sublytic C5b-9. In detail, the elements of C/EBP binding to rat IL-6 and TGF-1 promoter and 3 acetylated sites of rat C/EBP protein were first revealed. Furthermore, silencing the p300 or C/EBP gene in rat kidney significantly reduced the production of IL-6 and TGF-1 and renal lesions in Thy-1N rats. Together, these data indicate that the mechanism of IL-6 and TGF-1 production in renal tissue of Thy-1N rats is associated with sublytic C5b-9 up-regulated p300 and p300-mediated C/EBP acetylation as well as C/EBP-activated IL-6 and TGF-1 genes.Zhang, J., Li, Y., Shan, K., Wang, L., Qiu, W., Lu, Y., Zhao, D., Zhu, G., He, F., Wang, Y. Sublytic C5b-9 induces IL-6 and TGF-1 production by glomerular mesangial cells in rat Thy-1 nephritis through p300-mediated C/EBP acetylation.