Granulocyte-Macrophage Colony-Stimulating Factor (CSF) and Macrophage CSF-Dependent Macrophage Phenotypes Display Differences in Cytokine Profiles and Transcription Factor Activities: Implications for CSF Blockade in Inflammation
Open accessAbstract
GM-CSF and M-CSF (CSF-1) can enhance macrophage lineage numbers as well as modulate their differentiation and function. Of recent potential significance for the therapy of inflammatory/autoimmune diseases, their blockade in relevant animal models leads to a reduction in disease activity. What the critical actions are of these CSFs on macrophages during inflammatory reactions are unknown. To address this issue, adherent macrophages (GM-BMM and BMM) were first derived from murine bone marrow precursors by GM-CSF and M-CSF, respectively, and stimulated in vitro with LPS to measure secreted cytokine production, as well as NF-κB and AP-1 activities. GM-BMM preferentially produced TNF-α, IL-6, IL-12p70, and IL-23 whereas, conversely, BMM generated more IL-10 and CCL2; strikingly the latter population could not produce detectable IL-12p70 and IL-23. Following LPS stimulation, GM-BMM displayed rapid IκBα degradation, RelA nuclear translocation, and NF-κB DNA binding relative to BMM, as well as a faster and enhanced AP-1 activation. Each macrophage population was also pretreated with the other CSF before LPS stimulation and found to adopt the phenotype of the other population to some extent as judged by cytokine production and NF-κB activity. Thus, GM-CSF and M-CSF demonstrate, at the level of macrophage cytokine production, different and even competing responses with implications for their respective roles in inflammation, including a possible dampening or suppressive role for M-CSF in certain circumstances.
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CSF-1 and CSF-2 signaling represent opposing influences on the phenotype of macrophages, with CSF-1 being protective against inflammation.
“It has been also suggested that CSF-1 and CSF-2 signaling represent opposing influences on the phenotype of macrophages, with CSF-1 being protective against inflammation [12].”
From Loss of homeostatic microglial phenotype in CSF1R-related Leukoencephalopathy (2020) · cites this paper as [12]
M2 macrophages can be generated under conditions of MCSF stimulation in vitro.
“we took advantage of the reports that M2 macrophages can be generated under conditions of MCSF stimulation in vitro [39], [40].”
From Rac2 Controls Tumor Growth, Metastasis and M1-M2 Macrophage Differentiation In Vivo (2014) · cites this paper as [40]
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- Authors
- Fleetwood, A. J., Lawrence, T., Hamilton, J. A., & Cook, A. D.
- Affiliations
- The Royal Melbourne Hospital (AU)
- Imperial College London (GB)
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2007-04
- Volume
- 178
- Issue
- 8
- Pages
- 5245-5252
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W1942388905
- Cited by
- 607
- References
- 3
- Citations by year
- 2026: 14 · 2025: 27 · 2024: 17 · 2023: 35 · 2022: 37 · 2021: 46 · 2020: 45 · 2019: 35 · 2018: 30 · 2017: 39 · 2016: 41 · 2015: 39 · 2014: 67 · 2013: 39 · 2012: 27
- FWCI
- 5.46
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Immunology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
- Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Keywords
- GM-CSF, macrophage colony-stimulating factor, macrophage differentiation, macrophage phenotype, cytokine production, NF-κB activation, AP-1 activation, IκBα degradation, p65 nuclear translocation, lipopolysaccharide stimulation, inflammation, autoimmune disease, bone marrow-derived macrophages, IL-12p70, IL-23, IL-10, MCP-1, TNF-α, interleukin-6
- MeSH terms
- Animals, Cells, Cultured, DNA, Female, Inflammation, Lipopolysaccharides, Macrophages, Mice, Inbred C57BL, Phenotype, Macrophage Colony-Stimulating Factor, Granulocyte-Macrophage Colony-Stimulating Factor, Cytokines, NF-kappa B, Transcription Factor AP-1, Mice
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