Dilazep hydrochloride, an antiplatelet drug, inhibits lipopolysaccharide-induced mouse mesangial cell IL-6 secretion and proliferation.
BACKGROUND
Antiplatelet agents have been widely used to reduce proteinuria and to prevent the progression of chronic glomerulonephritis or diabetic nephropathy to end-stage renal failure. Dipyridamole, one type of antiplatelet drug, inhibits the proliferation of glomerular mesangial cells (MCs). The effect of dilazep hydrochloride (dilazep) on these cells is still obscure. The effects of dilazep on cultured MC IL-6 secretion and proliferation were investigated in the present study.


METHODS
IL-6 secretion from MC induced by bacterial lipopolysaccharide (LPS) were assessed using sandwich ELISA. LPS-induced MC proliferation was detected by 3H-thymidine incorporation and WST-1 assay (similar to MTT assay).


RESULTS
Incubation of MCs with various dosages of LPS (0, 1, 10, 50 and 100 ng/ml) induced IL-6 secretion in a dose-dependent manner. However, dilazep significantly inhibited this LPS-induced IL-6 secretion from MCs in a dose- and time-dependent manner. Dilazep also significantly inhibited MC proliferation in a dose-dependent manner.


CONCLUSIONS
It appears that these effects of dilazep may prevent progression of mesangial proliferative glomerulonephritis.
Gohda
T
T
Division of Nephrology, Department of Medicine, Juntendo University School of Medicine, Tokyo, Japan.
Makita
Y
Y
Shike
T
T
Funabiki
K
K
Shirato
I
I
Tomino
Y
Y
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D004109:Dilazep / Q000494:pharmacology*; D004336:Drug Antagonism; D005920:Glomerular Mesangium / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D015850:Interleukin-6 / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D051379:Mice; D014665:Vasodilator Agents / Q000494:pharmacology*
D015850:Interleukin-6; D008070:Lipopolysaccharides; D014665:Vasodilator Agents; D004109:Dilazep