Source: Annual Congress 2010 - Respiratory and peripheral muscles: From basic mechanisms to altered function

Abstract

Skeletal muscle atrophy is a prominent and disabling feature of inflammatory lung disease. The aims of this study were a) to investigate whether acute pulmonary inflammation is sufficient to induce systemic inflammation and loss of muscle mass, and b) assess whether muscle NF-κB activity is required for muscle atrophy.
C57/bl6 mice received a single bolus of E.coli LPS by intra-tracheal (IT) instillation to induce acute pulmonary inflammation, or 0.9% NaCl as a control.
Neutrophil infiltration in the lungs was maximal 48h post-LPS. Loss of bodyweight (bw) and muscle weight (mw) was maximal (10-15% decrease) 48h-72h post-LPS. mRNA expression of the muscle protein degradation regulating enzymes MuRF1 and atrogin-1 was increased in muscle, preceding maximal loss of mw. Systemic inflammation was evidenced by increased circulating levels of a number of cytokines and chemokines, as well as NF-κB activation in circulating neutrophils and skeletal muscle measured in NF-κB-luciferase reporter mice, which was verified by increased KC (IL-8) and IκBα expression in muscle. Importantly, muscle specific abrogation of NF-κB signaling in transgenic MISR mice strongly attenuated loss of muscle mass following IT-LPS instillation.
These data demonstrate that acute pulmonary inflammation induces systemic inflammation, and that subsequent muscular NF-κB activation contributes to muscle atrophy.
This work was supported by grants from the Organization for Scientific Research NWO (VENI 91656112) and the Dutch Top Institute Pharma (project # T1-201).

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Citations should be made in the following way:
R. Langen, A. Haegens, J. Vernooy, E. Wouters, A. Schols (Netherlands). Systemic inflammation and NF-κB-dependent muscle atrophy in response to acute pulmonary inflammation. Eur Respir J 2010; 36: Suppl. 54, 3406

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