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Probucol inhibits intercellular adhesion molecule‐1 expression on cultured rat mesangial cells
Author(s) -
SUGIURA Toshihiro,
WADA Akira,
YAMAUCHI Atsushi,
HORIO Masaru,
IMAI Enyu,
HORI Masatsugu
Publication year - 1998
Publication title -
nephrology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 61
eISSN - 1440-1797
pISSN - 1320-5358
DOI - 10.1111/j.1440-1797.1998.tb00324.x
Subject(s) - probucol , lipopolysaccharide , mesangial cell , messenger rna , intercellular adhesion molecule 1 , intracellular , medicine , endocrinology , glomerulonephritis , microbiology and biotechnology , inflammation , biology , biochemistry , kidney , cholesterol , gene
SUMMARY: Interleukin‐1 (IL‐1) has been reported to participate in the progression of glomerulonephritis by, in part, up‐regulating intercellular adhesion molecule‐1 (ICAM‐1) expression in experimental glomerulonephritis. In the present study, we examined whether probucol, an antihyperlipidemic agent, inhibited IL‐1‐induced inflammatory processes in mesangial cells in culture. Northern blot analysis demonstrated that 200 U/mL IL‐1 up‐regulated ICAM‐1 messenger RNA (mRNA) expression with its peak at 4‐6 h after stimulation. Ten μg/mL lipopolysaccharide (LPS), a stimulant to release IL‐1 from mesangial cells, induced ICAM‐1 mRNA expression by five‐fold within 6 h and 10 μg/mL probucol notably reduced this induction. Immunoblotting also confirmed that LPS increased ICAM‐1 protein by two‐fold within 24 h and probucol inhibited this increase. IL‐1 receptor antagonist (IL‐1ra; 1–100 ng/mL) suppressed LPS‐induced ICAM‐1 mRNA expression in a dose‐dependent manner and 100 ng/mL IL‐1ra completely inhibited ICAM‐1 induction, indicating that LPS increased ICAM‐1 expression through the action of secreted IL‐1. Interleukin‐1 activity in culture media, measured by thymocyte proliferation assay, was significantly enhanced by LPS and inhibited by probucol. However, neither LPS nor probucol substantially affected IL‐1 mRNA expression, suggesting that the IL‐1 activity might be regulated at post‐translational level. These results suggest that probucol may act as an anti‐inflammatory drug by suppressing IL‐1 activity from mesangial cells in the progression of glomerulonephritis.