Ex vivo lipopolysaccharide-induced interleukin-1 secretion from murine peritoneal macrophages inhibited by probucol, a hypocholesterolemic agent with antioxidant properties
| Autor: | Niall S. Doherty, Lisa F. Schmidt, George Ku, Robert J. Dinerstein, Richard L. Jackson |
|---|---|
| Rok vydání: | 1990 |
| Předmět: |
Interleukin 2
Lipopolysaccharides Lipopolysaccharide Probucol Prostaglandin Administration Oral Mice Inbred Strains Pharmacology Biochemistry Antioxidants chemistry.chemical_compound Mice Phenols Genetics medicine Animals Secretion Molecular Biology Peritoneal Cavity Triglycerides Interleukin 3 Tumor Necrosis Factor-alpha Macrophages Zymosan Interleukin Arthritis Experimental Rats Zinc Cholesterol chemistry Rats Inbred Lew Immunology Interleukin-2 Tumor necrosis factor alpha Interleukin-3 Secretory Rate Biotechnology medicine.drug Interleukin-1 |
| Zdroj: | FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 4(6) |
| ISSN: | 0892-6638 |
| Popis: | Probucol, 4,4'-(isopropylidenedithio)bis(2,6-di-tert-butyl-phenol), has been shown to inhibit atherogenesis in genetically hypercholesterolemic (Watanabe) rabbits. Since atherosclerotic lesions contain macrophages capable of screting interleukin 1 (IL 1) and other cytokines that could contribute to the pathogenesis of the disease, we have investigated whether probucol affects IL 1 secretion. Resident peritoneal macrophages from mice dosed with probucol secreted 40-80% less IL 1 than macrophages from control animals when stimulated in vitro with lipopolysaccharide (LPS). The inhibitory effect of probucol was observed when IL 1 was assayed by the standard bioassay, the thymocyte proliferation assay, or a competitive IL 1 receptor binding assay. Probucol treatment had no effect on LPS-induced membrane IL 1 expression; secretion of tumor necrosis factor (TNF); Con A-induced splenic interleukin 2 (IL 2) and interleukin 3 (IL 3) release; and prostaglandin- or zymosan-induced secretion of prostacyclin, leukotriene C4, acid phosphatase, or superoxide anion. In contrast to the effect of oral administration, direct addition of probucol to macrophage cultures did not inhibit IL 1 release. Probucol administration did, however, inhibit the fall in serum zinc level induced by intravenous injection of LPS in zymosan-primed mice but had no effect on the LPS-induced increase in serum triglyceride levels, which indirectly confirms that probucol administration inhibits IL 1 but not TNF secretion. Paw granuloma induced in mice by heat-killed mycobacteria was inhibited by oral administration of probucol, an effect that may be attributable to inhibition of IL 1 secretion. Probucol neither reduced zymosan-induced liver granulomata in mice nor inhibited adjuvant-induced arthritis in rats. We suggest that inhibition of IL 1 secretion from macrophages by probucol contributes to its therapeutic effects in atherosclerosis and may also result in beneficial activity in some chronic inflammatory diseases. |
| Databáze: | OpenAIRE |
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