ISSN:
1440-1797
Source:
Blackwell Publishing Journal Backfiles 1879-2005
Topics:
Medicine
Notes:
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.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1111/j.1440-1797.1998.tb00324.x
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