Macrophages augment the skeletal muscle proinflammatory response through TNFα following LPS-induced acute lung injury.

Autor: Bivona JJ 3rd; Department of Medicine, University of Vermont Larner College of Medicine, Burlington, VT, USA.; Cellular, Molecular, and Biomedical Sciences Doctoral Program, University of Vermont, Burlington, VT, USA., Crymble HM; Department of Medicine, University of Vermont Larner College of Medicine, Burlington, VT, USA., Guigni BA; Cellular, Molecular, and Biomedical Sciences Doctoral Program, University of Vermont, Burlington, VT, USA.; Department of Molecular Physiology and Biophysics, University of Vermont Larner College of Medicine, Burlington, VT, USA., Stapleton RD; Department of Medicine, University of Vermont Larner College of Medicine, Burlington, VT, USA., Files DC; Department of Internal Medicine, Section on Pulmonary, Critical Care, Allergy, and Immunology, Wake Forest School of Medicine, Winston-Salem, NC, USA., Toth MJ; Department of Medicine, University of Vermont Larner College of Medicine, Burlington, VT, USA.; Department of Molecular Physiology and Biophysics, University of Vermont Larner College of Medicine, Burlington, VT, USA., Poynter ME; Department of Medicine, University of Vermont Larner College of Medicine, Burlington, VT, USA., Suratt BT; Department of Medicine, University of Vermont Larner College of Medicine, Burlington, VT, USA.
Jazyk: angličtina
Zdroj: FASEB journal : official publication of the Federation of American Societies for Experimental Biology [FASEB J] 2021 Apr; Vol. 35 (4), pp. e21462.
DOI: 10.1096/fj.202002275RR
Abstrakt: Muscle may contribute to the systemic inflammatory environment during critical illness, but leukocyte interaction and cytokine influence on muscle and its response has not been fully explored in this context. Using an in vivo model of intratracheal lipopolysaccharide (IT LPS)-induced acute lung injury, we show that skeletal muscle rapidly responds with expression of proinflammatory genes, which may be explained by migration of LPS into the circulation. Treatment of mature C2C12 myotubes with LPS at a level achieved in the circulation following IT LPS elicited a proinflammatory cytokine expression profile similar to that of in vivo murine muscle following IT LPS. Stimulation with toll-like receptor (TLR) 2 and 3 agonists provoked comparable responses in C2C12 myotubes. Additionally, co-cultures of C2C12 myotubes and bone marrow-derived macrophages (BMDM) identified the capacity of macrophages to increase myotube proinflammatory gene expression, with tumor necrosis factor-α (TNFα) gene and protein expression largely attributable to BMDM. To investigate the contribution of TNFα in the synergy of the co-culture environment, C2C12 myotubes were treated with recombinant TNFα, co-cultures were established using TNF-deficient BMDM, and co-cultures were also depleted of TNFα using antibodies. To determine whether the in vitro observations were relevant in vivo, mice received intramuscular administration of LPS ± TNFα or TNFα-neutralizing antibodies and showed that TNFα is both sufficient and necessary to induce synergistic cytokine release from muscle. Taken together, these data demonstrate how skeletal muscle tissue may contribute proinflammatory cytokines following acute endotoxin injury and the potential of leukocytes to augment this response via TNFα secretion.
(© 2021 Federation of American Societies for Experimental Biology.)
Databáze: MEDLINE
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