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Recombinant human TNF induces production of granulocyte-monocyte colony-stimulating factor
Abstract:
Tumor necrosis factor (TNF) is synthesized by macrophages exposed to endotoxin. It produces haemorrhagic necrosis of a variety of tumours in mice and is cytostatic or cytocidal against various transformed cell lines in vitro, but viability of normal human or rodent cells is unaffected. The role of TNF is unlikely to be restricted to the rejection of tumours. Colony-stimulating factors (CSFs) are required for survival, proliferation and differentiation of haematopoietic progenitor cells. The haematopoietic growth factor known as granulocyte-monocyte colony-stimulating factor (GM-CSF) has the ability to stimulate proliferation and differentiation of normal granulocyte-monocyte and eosinophil stem cells and enhance the proliferation of pluripotent, megakaryocyte and erythroid stem cells. In addition, GM-CSF stimulates a variety of functional activities in mature granulocytes and macrophages, for example inhibition of migration, phagocytosis of microbes, oxidative metabolism, and antibody-dependent cytotoxic killing of tumour cells. We show here that TNF markedly stimulates production of GM-CSF messenger RNA and protein in normal human lung fibroblasts and vascular endothelial cells, and in cells of several malignant tissues.
Insights
Tumor necrosis factor (TNF) significantly boosts the production of granulocyte-monocyte colony-stimulating factor (GM-CSF) in various human cells, including normal fibroblasts and malignant tissues. This finding suggests a broader role for TNF beyond tumor rejection.
Area of Science:
- Immunology
- Cell Biology
- Molecular Biology
Background:
- Tumor necrosis factor (TNF) is a cytokine produced by macrophages, known for its anti-tumor properties.
- Colony-stimulating factors (CSFs), particularly granulocyte-monocyte colony-stimulating factor (GM-CSF), are crucial for hematopoietic cell survival, proliferation, and differentiation.
- GM-CSF also enhances the functional activities of mature granulocytes and macrophages.
Purpose of the Study:
- To investigate the effect of TNF on the production of GM-CSF.
- To determine if TNF influences GM-CSF production in various cell types, including normal and malignant cells.
Main Methods:
- Treatment of normal human lung fibroblasts and vascular endothelial cells with TNF.
- Analysis of GM-CSF messenger RNA (mRNA) and protein levels in treated cells.
- Examination of GM-CSF production in cells from malignant tissues.
Main Results:
- TNF markedly stimulates the production of GM-CSF mRNA and protein in normal human lung fibroblasts and vascular endothelial cells.
- Increased GM-CSF production was also observed in cells derived from several malignant tissues.
- These findings indicate that TNF can induce GM-CSF production across different cell types.
Conclusions:
- TNF plays a significant role in stimulating GM-CSF production.
- The interaction between TNF and GM-CSF suggests a potential link between tumor immunity and hematopoietic regulation.
- Further research is warranted to explore the implications of this interaction in various physiological and pathological contexts.