The DOI matches its Crossref record; 58 of the 58 references it cites were found in a registry or an index.
Macrophage glucocorticoid receptors regulate Toll-like receptor 4-mediated inflammatory responses by selective inhibition of p38 MAP kinase
Open accessAbstract
To explore the role of glucocorticoids in regulation of kinase pathways during innate immune responses, we generated mice with conditional deletion of glucocorticoid receptor (GR) in macrophages (MGRKO). Activation of toll-like receptor 4 (TLR4) by lipopolysaccharide (LPS) caused greater mortality and cytokine production in MGRKO mice than in controls. Ex vivo, treatment with dexamethasone (Dex) markedly inhibited LPS-mediated induction of inflammatory genes in control but not GR-deficient macrophages. We show that Dex inhibits p38 MAPK, but not PI3K/Akt, ERK, or JNK, in control macrophages. Associated with p38 inhibition, Dex induced MAP kinase phosphatase-1 (MKP-1) in control, but not MGRKO, macrophages. Consistent with the ex vivo studies, treatment with a p38 MAPK-specific inhibitor resulted in rescue of MGRKO mice from LPS-induced lethality. Taken together, we identify p38 MAPK and its downstream targets as essential for GR-mediated immunosuppression in macrophages.
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“The single point mutation A458T engineered in GRdim is thus unlikely to fully abrogate the formation of functional GR homodimers (30, 112, 113).”
From The HPA – Immune Axis and the Immunomodulatory Actions of Glucocorticoids in the Brain (2014) · cites this paper as [113]
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Metadata
- Authors
- Bhattacharyya, S., Brown, D. E., Brewer, J. A., Vogt, S. K., & Muglia, L. J.
- Affiliations
- Departments of Pediatrics
- Washington University in St. Louis (US)
- ORCID
- Muglia, Louis J.
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2007-01-25
- Volume
- 109
- Issue
- 10
- Pages
- 4313-4319
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- PMC
- PMC1885507
- OpenAlex
- W2104547539
- Cited by
- 249
- References
- 58
- Citations by year
- 2026: 7 · 2025: 11 · 2024: 9 · 2023: 15 · 2022: 13 · 2021: 11 · 2020: 20 · 2019: 15 · 2018: 10 · 2017: 23 · 2016: 6 · 2015: 15 · 2014: 12 · 2013: 12 · 2012: 11
- FWCI
- 5.70
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Blood (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Allergy and Infectious Diseases (AI50655, R01AI050655, R21AI050655)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Endocrinology › Estrogen and related hormone effects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
- Keywords
- glucocorticoid receptor, macrophages, TLR4, p38 MAPK, dexamethasone, lipopolysaccharide, MKP-1, immunosuppression, innate immunity, inflammatory cytokines, conditional knockout mice, PI3K/Akt, ERK, JNK
- MeSH terms
- Animals, Dexamethasone, Enzyme Inhibitors, Inflammation, Lipopolysaccharides, Macrophages, Mice, Inbred C57BL, Models, Biological, Phosphoprotein Phosphatases, Receptors, Glucocorticoid, Cytokines, Protein Tyrosine Phosphatases, Immediate-Early Proteins, Mice, Knockout, Cell Cycle Proteins, Inflammation Mediators, p38 Mitogen-Activated Protein Kinases, Toll-Like Receptor 4, Mice, Dual Specificity Phosphatase 1, Protein Phosphatase 1
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