Muscle wasting and impaired muscle regeneration in a murine model of chronic pulmonary inflammation

  • Langen R
  • Schols A
  • Kelders M
 et al. 
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Muscle wasting and increased circulating levels of inflammatory cytokines, including TNF-alpha, are common features of chronic obstructive pulmonary disease. To investigate whether inflammation of the lung is responsible for systemic inflammation and muscle wasting, we adopted a mouse model of pulmonary inflammation resulting from directed overexpression of a TNF-alpha transgene controlled by the surfactant protein C (SP-C) promoter. Compared with wild-type mice, SP-C/TNF-alpha mice exhibited increased levels of TNF-alpha in the circulation and increased endogenous TNF-alpha expression in skeletal muscle, potentially reflecting an amplificatory response to circulating TNF-alpha. Decreased muscle and body weights observed in SP-C/TNF-alpha mice were indicative of muscle wasting. Further evaluation of the SP-C/TNF-alpha mouse musculature revealed a decreased muscle regenerative capacity, shown by attenuated myoblast proliferation and differentiation in response to reloading of disuse-atrophied muscle, which may contribute to skeletal muscle wasting. Importantly, incubation of cultured myoblasts with TNF-alpha also resulted in elevated TNF-alpha mRNA levels and inhibition of myoblast differentiation. Collectively, our results demonstrate that chronic pulmonary inflammation results in muscle wasting and impaired muscle regeneration in SP-C/TNF-alpha mice, possibly as a consequence of an amplificatory TNF-alpha expression circuit extending from the lung to skeletal muscle

Author-supplied keywords

  • 0
  • A
  • Animals
  • As
  • Attenuated
  • Body Weight
  • Cell Differentiation
  • Cell Line
  • Cell Proliferation
  • Chronic
  • Chronic Disease
  • Chronic Obstructive
  • Common
  • Cultured
  • Cytokine
  • Cytokines
  • Differentiation
  • Disease
  • Disease Models,Animal
  • Factor
  • Heavy Chain
  • Heavy-Chain
  • Histones
  • Inflammation
  • Lung
  • Messenger
  • Mice
  • Mice,Inbred C57BL
  • Mice,Transgenic
  • Muscle
  • Muscular Atrophy
  • Myoblasts
  • Myoblasts,Skeletal
  • Myosin Heavy Chains
  • Necrosis
  • Netherlands
  • Obstructive
  • Organ Size
  • Pneumonia
  • Promoter Regions (Genetics)
  • Protein
  • Pulmonary
  • Pulmonary Disease
  • Pulmonary Surfactant-Associated Protein C
  • RNA
  • RNA,Messenger
  • Receptor
  • Receptors
  • Receptors,Tumor Necrosis Factor,Type II
  • Regeneration
  • Rn
  • Sb
  • Skeletal
  • Systemic
  • Tumor
  • Tumor Necrosis Factor
  • Tumor Necrosis Factor-alpha
  • Universities
  • an
  • blood
  • chronic obstructive pulmonary disease
  • circulation
  • complications
  • drug effects
  • etiology
  • genetics
  • im
  • in
  • inhibition
  • metabolism
  • muscle,skeletal
  • overexpression
  • pathology
  • pharmacology
  • physiopathology
  • proliferation
  • the Netherlands

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  • PMID: 16794259


  • R C Langen

  • A M Schols

  • M C Kelders

  • der V van

  • E F Wouters

  • Y M Janssen-Heininger

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