Influenza A Virus Infection Induces Muscle Wasting via IL-6 Regulation of the E3 Ubiquitin Ligase Atrogin-1
- 15 January 2019
- journal article
- research article
- Published by The American Association of Immunologists in The Journal of Immunology
- Vol. 202 (2), 484-493
- https://doi.org/10.4049/jimmunol.1701433
Abstract
Muscle dysfunction is common in patients with adult respiratory distress syndrome and is associated with morbidity that can persist for years after discharge. In a mouse model of severe influenza A pneumonia, we found the proinflammatory cytokine IL-6 was necessary for the development of muscle dysfunction. Treatment with a Food and Drug Administration–approved Ab antagonist to the IL-6R (tocilizumab) attenuated the severity of influenza A–induced muscle dysfunction. In cultured myotubes, IL-6 promoted muscle degradation via JAK/STAT, FOXO3a, and atrogin-1 upregulation. Consistent with these findings, atrogin-1+/− and atrogin-1−/− mice had attenuated muscle dysfunction following influenza infection. Our data suggest that inflammatory endocrine signals originating from the injured lung activate signaling pathways in the muscle that induce dysfunction. Inhibiting these pathways may limit morbidity in patients with influenza A pneumonia and adult respiratory distress syndrome.Keywords
This publication has 71 references indexed in Scilit:
- Fiji: an open-source platform for biological-image analysisNature Methods, 2012
- Acute Respiratory Distress Syndrome Induced by a Swine 2009 H1N1 Variant in MicePLOS ONE, 2012
- Functional Disability 5 Years after Acute Respiratory Distress SyndromeThe New England Journal of Medicine, 2011
- Influenza virus activates inflammasomes via its intracellular M2 ion channelNature Immunology, 2010
- The Intracellular Sensor NLRP3 Mediates Key Innate and Healing Responses to Influenza A Virus via the Regulation of Caspase-1Immunity, 2009
- The NLRP3 Inflammasome Mediates In Vivo Innate Immunity to Influenza A Virus through Recognition of Viral RNAImmunity, 2009
- Skeletal muscle growth in young rats is inhibited by chronic exposure to IL-6 but preserved by concurrent voluntary endurance exerciseJournal of Applied Physiology, 2009
- Muscle wasting and interleukin-6-induced atrogin-I expression in the cachectic Apc Min/+ mousePflügers Archiv - European Journal of Physiology, 2008
- Ambient particulate matter accelerates coagulation via an IL-6–dependent pathwayJCI Insight, 2007
- A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye bindingAnalytical Biochemistry, 1976