Differential inhibition of IL-1 alpha and TNF-alpha generation by ammonium metavanadate in murine macrophages.
The relationship between immunotoxicity of ammonium metavanadate (NH4VO3) and levels of tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 (IL-1) was studied with a NH4VO3-treated murine macrophage-like cell line, 1774 and resident peritoneal macrophages (PEM) obtained from treated mice. Lipopolysaccharide (LPS)-induced elevation of extracellular TNF-alpha in PEM and 1774 cells was not markedly affected by prior treatment with vanadate. However, PEM from treated mice at 10 mg V/kg (10V) had a significantly lower level of LPS-induced intracellular TNF-alpha. NH4VO3-treated 1774 cells at 3.6 (V1) and 7.2 micrograms V/10(7) cells (V2) had significantly higher levels of intracellular TNF-alpha than the PO4 and V3 (10.8 micrograms V/10(7) cells) groups. Although the four PEM groups showed no marked difference in extracellular IL-1 alpha levels, PEM from treated mice at 2.5V and 10V had significantly lower levels of intracellular IL-1 alpha than those from control groups. 1774 cells from PO4 and NH4Cl groups showed significant increases in intracellular IL-1 alpha following treatment with LPS. However, 1774 cells with prior treatment with vanadate revealed significant reduction in levels of LPS-induced intracellular IL-1 alpha when compared to control groups. Therefore, the previously reported reduced resistance of vanadate-treated mice to Listeria monocytogenes could be attributed to an inhibitory effect on the production of IL-1 alpha in macrophages.
Vaddi
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Du Pont Merck Pharmaceutical Company, Wilmington, Delaware, USA.
Wei
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D000818:Animals; D002460:Cell Line; D005260:Female; D007107:Immune System / Q000187:drug effects; D007375:Interleukin-1 / Q000032:analysis / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D008264:Macrophages / Q000187:drug effects*; D017737:Macrophages, Peritoneal / Q000187:drug effects; D051379:Mice; D015398:Signal Transduction / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D014638:Vanadates / Q000633:toxicity*
D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D014638:Vanadates; C101036:ammonium metavanadate