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Isolation Protocol of Mouse Monocyte-derived Dendritic Cells and Their Subsequent In Vitro Activation with Tumor Immune Complexes
Published on: May 31, 2018
The effects of tumor necrosis factor on the production of interleukin-1 by macrophages
Abstract:
We investigated the effect of tumor necrosis factor (TNF) on interleukin-1 (IL-1) production by mouse macrophages. At high doses of TNF, macrophages produced no IL-1 (as judged in the LAF assay) even when exposed to bacterial lipopolysaccharide (LPS), an excellent inducer of IL-1 production. In lower (picogram/ml) doses, TNF caused macrophages to make factors which showed modest activity in the LAF assay and that activity could be blocked by antibody to IL-1. TNF induces in low doses also the production of a factor(s) which synergizes with IL-1 in the LAF assay.
Insights
Tumor necrosis factor (TNF) significantly impacts interleukin-1 (IL-1) production in mouse macrophages. High TNF doses inhibit IL-1, while low doses induce synergistic factors and modest IL-1 activity.
Area of Science:
- Immunology
- Cell Biology
- Inflammation Research
Background:
- Interleukin-1 (IL-1) is a key cytokine in inflammatory responses.
- Tumor Necrosis Factor (TNF) is a pro-inflammatory cytokine with complex regulatory roles.
- Macrophages are critical immune cells involved in producing inflammatory mediators.
Purpose of the Study:
- To investigate the dose-dependent effects of TNF on IL-1 production by mouse macrophages.
- To characterize the nature of factors induced by TNF in macrophages.
- To understand the interaction between TNF and IL-1 signaling pathways.
Main Methods:
- Primary mouse macrophage cultures.
- Stimulation with varying doses of TNF and bacterial lipopolysaccharide (LPS).
- Quantification of IL-1 production using the LAF assay.
- Neutralization of IL-1 activity with specific antibodies.
Main Results:
- High doses of TNF completely suppressed LPS-induced IL-1 production.
- Low doses of TNF induced factors with modest IL-1-like activity, blockable by anti-IL-1 antibodies.
- Low doses of TNF also induced factors that synergize with IL-1 in the LAF assay.
Conclusions:
- TNF exhibits a dose-dependent regulatory effect on IL-1 production in macrophages.
- TNF can inhibit IL-1 production at high concentrations.
- At low concentrations, TNF modulates IL-1 activity and induces synergistic factors, suggesting a complex role in immune regulation.
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