Macrophages augment the skeletal muscle proinflammatory response through TNFα following LPS‐induced acute lung injury, 2021 Joseph J. Bivona

Mij · Mar 22, 2021

Abstract
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.
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https://faseb.onlinelibrary.wiley.com/doi/10.1096/fj.202002275RR

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Macrophages augment the skeletal muscle proinflammatory response through TNFα following LPS‐induced acute lung injury, 2021 Joseph J. Bivona

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Macrophages augment the skeletal muscle proinflammatory response through TNFα following LPS‐induced acute lung injury, 2021 Joseph J. Bivona

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