title: Effect of pulmonary TNF-α overexpression on mouse isolated skeletal muscle function.
abstract: TNF-α is a proinflammatory cytokine that is involved in numerous pathological processes including chronic obstructive pulmonary disease (COPD). In the present study, we used a transgenic mouse model that overexpresses TNF-α in the lung (Tg(+)) to test the hypothesis that chronic exposure to TNF-α (as seen in COPD) reduces skeletal muscle force production and fatigue resistance, particularly under low Po(2) conditions. At 7-12 mo, body and muscle weight of both extensor digitorum longus (EDL) and soleus were significantly smaller in Tg(+) compared with littermate wild-type (WT) mice; however, the body-to-muscle weight ratio was not different between groups. EDL and soleus muscles were subjected to in vitro fatiguing contractile periods under high (∼550 Torr) and low Po(2) (∼40 Torr). Although all muscles were less fatigue-resistant during low Po(2) compared with high Po(2), only the soleus fatigued more rapidly in Tg(+) mice (∼12%) compared with WT at high Po(2). The maximal tension of EDL was equally reduced in Tg(+) mice (28-34% decrease from WT under both Po(2) conditions); but for soleus this parameter was smaller only under low Po(2) in Tg(+) mice (∼31% decrease from WT). The peak rate of relaxation and the peak rate of contraction were both significantly reduced in Tg(+) EDL muscles compared with WT EDL under low Po(2) conditions, but not in soleus. These results demonstrate that TNF-α upregulation in the lung impairs peripheral skeletal muscle function but affects fast- and slow-twitch muscles differentially at high and low Po(2).
authors.affiliation: Dept. of Medicine, Univ. of California, San Diego, 9500 Gilman Dr., La Jolla, CA 92093-0623, USA. lzuo@ucsd.edu
authors.forename: Li
authors.initials: L
authors.lastname: Zuo
authors.forename: Leonardo
authors.initials: L
authors.lastname: Nogueira
authors.forename: Michael C
authors.initials: MC
authors.lastname: Hogan
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004558:Electric Stimulation; D008168:Lung / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009119:Muscle Contraction / Q000502:physiology; D018656:Muscle Fibers, Fast-Twitch / Q000378:metabolism; D018657:Muscle Fibers, Slow-Twitch / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism; D029424:Pulmonary Disease, Chronic Obstructive / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism*
chemical_list: D014409:Tumor Necrosis Factor-alpha; D010100:Oxygen