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Counter Regulation of Spic by NF-κB and STAT Signaling Controls Inflammation and Iron Metabolism in Macrophages
- Source :
- Cell Reports, Vol 31, Iss 13, Pp 107825-(2020)
- Publication Year :
- 2020
- Publisher :
- Elsevier BV, 2020.
-
Abstract
- Summary: Activated macrophages must carefully calibrate their inflammatory responses to balance efficient pathogen control with inflammation-mediated tissue damage, but the molecular underpinnings of this “balancing act” remain unclear. Using genetically engineered mouse models and primary macrophage cultures, we show that Toll-like receptor (TLR) signaling induces the expression of the transcription factor Spic selectively in patrolling monocytes and tissue macrophages by a nuclear factor κB (NF-κB)-dependent mechanism. Functionally, Spic downregulates pro-inflammatory cytokines and promotes iron efflux by regulating ferroportin expression in activated macrophages. Notably, interferon-gamma blocks Spic expression in a STAT1-dependent manner. High levels of interferon-gamma are indicative of ongoing infection, and in its absence, activated macrophages appear to engage a “default” Spic-dependent anti-inflammatory pathway. We also provide evidence for the engagement of this pathway in sterile inflammation. Taken together, our findings uncover a pathway wherein counter-regulation of Spic by NF-κB and STATs attune inflammatory responses and iron metabolism in macrophages.
- Subjects :
- Male
0301 basic medicine
Iron
Ferroportin
Down-Regulation
Inflammation
Heme
Biology
Ligands
NF-κB
Monocytes
General Biochemistry, Genetics and Molecular Biology
Interferon-gamma
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
medicine
Animals
Macrophage
Spic
Interferon gamma
Receptor
lcsh:QH301-705.5
Transcription factor
Macrophages
Toll-Like Receptors
NF-kappa B
Biological Transport
Macrophage Activation
Cell biology
DNA-Binding Proteins
Mice, Inbred C57BL
STAT Transcription Factors
030104 developmental biology
lcsh:Biology (General)
chemistry
biology.protein
Bach1
Female
medicine.symptom
030217 neurology & neurosurgery
Signal Transduction
medicine.drug
Subjects
Details
- ISSN :
- 22111247
- Volume :
- 31
- Database :
- OpenAIRE
- Journal :
- Cell Reports
- Accession number :
- edsair.doi.dedup.....e06af5031e5465e8c38d689a5728d51c