Journal article
Stamp2 Controls Macrophage Inflammation through Nicotinamide Adenine Dinucleotide Phosphate Homeostasis and Protects against Atherosclerosis
Cell metabolism, Vol.16(1), pp.81-89
07/03/2012
DOI: 10.1016/j.cmet.2012.05.009
PMCID: PMC4163924
PMID: 22704678
Abstract
The six-transmembrane protein Stamp2 plays an important role in metabolically triggered inflammation and insulin action. We report that Stamp2 is expressed in human and mouse macrophages, is regulated upon differentiation or activation, acts as an anti-inflammatory protein, and regulates foam cell formation. Absence of Stamp2 results in significant increases in cellular NADPH levels, and both NADPH homeostasis and the exaggerated inflammatory response of Stamp2−/− macrophages are rescued by exogenous wild-type but not by a reductase-deficient Stamp2 molecule. Chemical and genetic suppression of NADPH production in Stamp2−/− macrophages reverts the heightened inflammatory response. Stamp2 is detected in mouse and human atherosclerotic plaques, and its deficiency promotes atherosclerosis in mice. Furthermore, bone marrow transplantation experiments demonstrated that Stamp2 in myeloid cells is sufficient to protect against atherosclerosis. Our data reveal a role of Stamp2 in controlling intermediary metabolites to regulate inflammatory responses in macrophages and in progression of atherosclerosis.
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► Stamp2 regulates NADPH metabolism and inflammatory responses in macrophages ► Stamp2's oxidoreductase domain is critical for control of the inflammatory responses ► Stamp2 deficiency promotes foam cell formation due to reduced cholesterol efflux ► Total body or myeloid Stamp2 deficiency in mice promotes atherosclerosis
Details
- Title: Subtitle
- Stamp2 Controls Macrophage Inflammation through Nicotinamide Adenine Dinucleotide Phosphate Homeostasis and Protects against Atherosclerosis
- Creators
- Henrik ten Freyhaus - Departments of Genetics and Complex Diseases, Harvard School of Public Health, Boston, MA 02115, USAEdiz S Calay - Departments of Genetics and Complex Diseases, Harvard School of Public Health, Boston, MA 02115, USAAbdullah Yalcin - Departments of Genetics and Complex Diseases, Harvard School of Public Health, Boston, MA 02115, USASara N Vallerie - Departments of Genetics and Complex Diseases, Harvard School of Public Health, Boston, MA 02115, USALing Yang - Departments of Genetics and Complex Diseases, Harvard School of Public Health, Boston, MA 02115, USAZerrin Z Calay - ETA Pathology and Cytology Lab, Istanbul 34365, TurkeyFahri Saatcioglu - Molecular Biosciences, University of Oslo, Oslo 0316, NorwayGökhan S Hotamisligil - Departments of Genetics and Complex Diseases, Harvard School of Public Health, Boston, MA 02115, USA
- Resource Type
- Journal article
- Publication Details
- Cell metabolism, Vol.16(1), pp.81-89
- Publisher
- Elsevier Inc
- DOI
- 10.1016/j.cmet.2012.05.009
- PMID
- 22704678
- PMCID
- PMC4163924
- ISSN
- 1550-4131
- eISSN
- 1932-7420
- Language
- English
- Date published
- 07/03/2012
- Academic Unit
- Molecular Physiology and Biophysics; Anatomy and Cell Biology
- Record Identifier
- 9984025470302771
Metrics
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