Muscle wasting and increased circulating levels of inflammatory cytokines, including tumor necrosis factor alpha (TNFalpha) are common features of COPD. To investigate if inflammation of the lung is responsible for systemic inflammation and muscle wasting, we adopted a mouse model of pulmonary inflammation resulting from directed over-expression of a TNFalpha transgene controlled by the surfactant protein C (SP-C) promoter. Compared to wild type, SP-C/TNFalpha mice exhibited increased levels of TNFalpha in the circulation and increased endogenous TNFalpha expression in skeletal muscle, potentially reflecting an amplificatory response to circulating TNFalpha. Decreased muscle and body weights observed in SP-C/TNFalpha mice were indicative of muscle wasting. Further evaluation of the SP-C/TNFalpha mouse musculature revealed a decreased muscle regenerative capacity, evidenced 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 TNFalpha also resulted in elevated TNFalpha 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/TNFalpha mice, possibly as a consequence of an amplificatory TNFalpha expression circuit extending from the lung to skeletal muscle.
|Journal||American Journal of Respiratory Cell and Molecular Biology|
|Publication status||Published - 1 Jan 2006|
Langen, R. C., Schols, A. M., Kelders, M. C., van der Velden, A. L. J., Wouters, E. F., & Janssen, Y. M. W. (2006). Muscle Wasting and Impaired Muscle Regeneration in a Murine Model of Chronic Pulmonary Inflammation. American Journal of Respiratory Cell and Molecular Biology, 35(6), 689-696. https://doi.org/10.1165/rcmb.2006-0103OC