ANGIOTENSIN-II STIMULATES INTERLEUKIN-6 RELEASE FROM CULTURED MOUSE MESANGIAL CELLS

Interleukin-6 (IL-6) is a multifunctional cytokine exerting a wide variety of biologic responses, including cell proliferation, Recently, IL-6 has been known to play a role in the pathogenesis of mesangial proliferative glomerulonephritis. IL-6 is now recognized as an autocrine growth factor for glomerular mesangial cells, and various inflammatory mediators have been shown to promote IL-6 release from mesangial cells. However, little is known about the noninflammatory stimuli of IL-6 release from mesangial cells, In this study, it was hypothesized that angiotensin II (AngII) is one of the noninflammatory mediators of IL-6 release in mesangial cells, and the effects of AngII on IL-6 release and mRNA expression in cultured mouse mesangial cells (CMMC) were investigated, It was demonstrated that AngII (10(-7) M or higher) caused IL-6 release and mRNA accumulation in CMMC. IL-6 release was detected at 4 h and reached a plateau at 8 h after the addition of AngII, whereas IL-6 mRNA expression peaked at 4 h, The effects of AngII on IL-6 release and gene expression were completely blocked by the AngII receptor type 1 (AT1 receptor) antagonist CV-11974. AngII and IL-6 were both shown to stimulate DNA synthesis in CMMC, and the blockade of IL-6 signaling with anti-IL-6 receptor antibody abolished the enhanced DNA synthesis induced by AngII, These results raise a possibility that the growth-promoting effect of AngII on mesangial cells is at least partially mediated by IL-6 released from mesangial cells.