Nicardipine hydrochloride suppresses DNA synthesis in human mesangial cells stimulated with recombinant human (rh) platelet-derived growth factor AA, rh interleukin-1 alpha, or rh tumor necrosis factor-alpha.

Abstract

In order to define the role of cytokines in mesangial cell pathophysiology, we measured the mitogenic activity of recombinant human platelet-derived growth factor AA (rhPDGF-AA), rh interleukin-1 alpha (rhIL-1 alpha) and rh tumor necrosis factor-alpha (rhTNF-alpha) in cultured human mesangial cells, and investigated the effect of the calcium channel blocker nicardipine hydrochloride on their cell mitogenic activity. DNA synthesis in mesangial cells, stimulated by rhPDGF-AA, rhIL-1 alpha or rhTNF-alpha, was measured using [3H]TdR up take and similar investigations, with nicardipine hydrochloride added to the above, were conducted. The results showed DNA synthesis in cultured human mesangial cells were stimulated by rhPDGF-AA, rhIL-1 alpha and rhTNF-alpha, and this effect was reduced by the addition of nicardipine hydrochloride. Since rhPDGF-AA, rhIL-1 alpha and rhTNF-alpha are released by the inflammatory cells which infiltrate glomeruli, these cytokines may be involved in the mechanisms of mesangial cell proliferation observed in immune-mediated mesangial proliferative glomerulonephritis. Nicardipine hydrochloride reduced DNA synthesis in cultured human mesangial cells in response to these cytokines, suggesting possible application in medical therapy for immune-mediated mesangial proliferative glomerulonephritis.