Interferon {gamma} (IFN-{gamma}) Augments Angiotensinogen (AGT) and Angiotensin Converting Enzyme (ACE) Expression in Rat Mesangial Cells (MCs)

Intrarenal angiotensin II accelerates renal injury accompanied with augmentation of T cell infiltration and IFN‐γ. IFN‐γ increases monocyte chemoattractant protein‐1 (MCP‐1) through STAT1 activation in MCs. However, the contribution of IFN‐γ to expression of renin‐angiotensin system (RAS) components in MCs has not been established. This study was performed to test the hypothesis that IFN‐γ augments AGT and ACE expression in MCs. Primary cultured MCs were treated with 0‐20 ng/ml IFN‐γ for 24 h. Activation of STAT1 and MCP‐1, AGT and ACE expression were evaluated by real‐time RT‐PCR and western blot analysis. IFN‐γ induced phosphorylation, translocalization of STAT1 to the nucleus, and MCP‐1 expression (8.99±0.77, relative ratio). Two ng/ml IFN‐γ increased AGT expression (1.54±0.07 in mRNA, 1.56±0.15 in protein, relative ratio). Moreover, 20 ng/ml IFN‐γ increased ACE expression (9.46±0.78 in mRNA, 2.65±0.60 in protein, relative ratio). These results indicate that IFN‐γ activates not only a proinflammatory cytokine but also RAS in MCs, which may lead to the development of glomerular damage. NIDDK/NIH (R01DK072408), NCRR/NIH (P20RR017659), NHLBI/NIH (R01HL026371)