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.
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.
Oda
H
H
Second Department of Internal Medicine, Hiroshima University School of Medicine, Japan.
Yorioka
N
N
Ito
T
T
Yamashita
K
K
Kushihata
S
S
Yamakido
M
M
D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D004247:DNA / Q000096:biosynthesis*; D003864:Depression, Chemical; D005920:Glomerular Mesangium / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D007536:Isomerism; D008934:Mitogens / Q000494:pharmacology; D009529:Nicardipine / Q000494:pharmacology*; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D011994:Recombinant Proteins / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D002121:Calcium Channel Blockers; D016207:Cytokines; D007375:Interleukin-1; D008934:Mitogens; D010982:Platelet-Derived Growth Factor; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D004247:DNA; D009529:Nicardipine