title: The peroxisome proliferator-activated receptor γ coactivator 1α/β (PGC-1) coactivators repress the transcriptional activity of NF-κB in skeletal muscle cells.
abstract: A persistent, low-grade inflammation accompanies many chronic diseases that are promoted by physical inactivity and improved by exercise. The beneficial effects of exercise are mediated in large part by peroxisome proliferator-activated receptor γ coactivator (PGC) 1α, whereas its loss correlates with propagation of local and systemic inflammatory markers. We examined the influence of PGC-1α and the related PGC-1β on inflammatory cytokines upon stimulation of muscle cells with TNFα, Toll-like receptor agonists, and free fatty acids. PGC-1s differentially repressed expression of proinflammatory cytokines by targeting NF-κB signaling. Interestingly, PGC-1α and PGC-1β both reduced phoshorylation of the NF-κB family member p65 and thereby its transcriptional activation potential. Taken together, the data presented here show that the PGC-1 coactivators are able to constrain inflammatory events in muscle cells and provide a molecular link between metabolic and immune pathways. The PGC-1s therefore represent attractive targets to not only improve metabolic health in diseases like type 2 diabetes but also to limit the detrimental, low-grade inflammation in these patients.
authors.affiliation: Biozentrum, Division of Pharmacology/Neurobiology, University of Basel, CH-4056 Basel, Switzerland.
authors.forename: Petra S
authors.initials: PS
authors.lastname: Eisele
authors.forename: Silvia
authors.initials: S
authors.lastname: Salatino
authors.forename: Jens
authors.initials: J
authors.lastname: Sobek
authors.forename: Michael O
authors.initials: MO
authors.lastname: Hottiger
authors.forename: Christoph
authors.initials: C
authors.lastname: Handschin
mesh_terms: D000818:Animals; D002460:Cell Line; D002908:Chronic Disease; D016207:Cytokines / Q000378:metabolism; D018450:Disease Progression; D005786:Gene Expression Regulation; D007249:Inflammation; D051379:Mice; D018485:Muscle Fibers, Skeletal / Q000378:metabolism; D018482:Muscle, Skeletal / Q000166:cytology / Q000378:metabolism*; D009132:Muscles / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D010805:Physical Conditioning, Animal; D015534:Trans-Activators / Q000378:metabolism*; D014157:Transcription Factors
chemical_list: D016207:Cytokines; D016328:NF-kappa B; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C485290:Ppargc1a protein, mouse; D015534:Trans-Activators; D014157:Transcription Factors