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Differential inhibition of IL-1 alpha and TNF-alpha generation by ammonium metavanadate in murine macrophages
Abstract:
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.
Insights
Ammonium metavanadate exposure alters macrophage cytokine production, potentially explaining reduced resistance to Listeria monocytogenes. This study investigated immunotoxicity by examining tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 (IL-1) levels in macrophages.
Area of Science:
- Immunotoxicology
- Cellular immunology
- Macrophage biology
Background:
- Ammonium metavanadate (NH4VO3) is known to cause immunotoxicity.
- Tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 (IL-1) are key cytokines involved in immune responses.
- Macrophages play a critical role in host defense against pathogens like Listeria monocytogenes.
Purpose of the Study:
- To investigate the relationship between ammonium metavanadate (NH4VO3) immunotoxicity and the levels of TNF-alpha and IL-1.
- To determine the effect of NH4VO3 exposure on both intracellular and extracellular cytokine production in macrophages.
- To elucidate the mechanism behind the reduced resistance of vanadate-treated mice to Listeria monocytogenes.
Main Methods:
- Utilized a murine macrophage-like cell line (1774) and primary resident peritoneal macrophages (PEM) from NH4VO3-treated mice.
- Stimulated cells with lipopolysaccharide (LPS) to induce cytokine production.
- Quantified intracellular and extracellular levels of TNF-alpha and IL-1 alpha using various treatment concentrations of NH4VO3.
Main Results:
- Extracellular TNF-alpha levels were largely unaffected by vanadate treatment.
- Intracellular TNF-alpha showed varied responses: decreased in PEM at 10 mg V/kg but increased in 1774 cells at lower vanadate concentrations.
- Intracellular IL-1 alpha levels were significantly reduced in both PEM and 1774 cells following vanadate exposure and LPS stimulation, suggesting an inhibitory effect.
Conclusions:
- Ammonium metavanadate exposure significantly inhibits intracellular interleukin-1 alpha production in macrophages.
- The observed reduction in IL-1 alpha may underlie the decreased resistance to Listeria monocytogenes infections in vanadate-treated mice.
- Vanadate's impact on macrophage cytokine profiles highlights its immunotoxic potential and its interference with crucial immune signaling pathways.
