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J Physiol Volume 586, Number 8, 2195-2201, April 15, 2008 DOI: 10.1113/jphysiol.2007.149781
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SKELETAL MUSCLE AND EXERCISE

Exercise induces expression of leukaemia inhibitory factor in human skeletal muscle

Christa Broholm1, Ole Hartvig Mortensen1, Søren Nielsen1, Thorbjorn Akerstrom1, Alaa Zankari1, Benny Dahl2 and Bente Klarlund Pedersen1

1 Centre of Inflammation and Metabolism, Department of Infectious Diseases
2 Department of Orthopaedic Surgery, Rigshospitalet, Faculty of Health Sciences, University of Copenhagen, Denmark

The leukaemia inhibitory factor (LIF) belongs to the interleukin (IL)-6 cytokine superfamily and is constitutively expressed in skeletal muscle. We tested the hypothesis that LIF expression in human skeletal muscle is regulated by exercise. Fifteen healthy young male volunteers performed either 3 h of cycle ergometer exercise at ~60% of Formula (n = 8) or rested (n = 7). Muscle biopsies were obtained from the vastus lateralis prior to exercise, immediately after exercise, and at 1.5, 3, 6 and 24 h post exercise. Control subjects had biopsy samples taken at the same time points as during the exercise trial. Skeletal muscle LIF mRNA increased immediately after the exercise and declined gradually during recovery. However, LIF protein was unchanged at the investigated time points. Moreover, we tested the hypothesis that LIF mRNA and protein expressions are modulated by calcium (Ca2+) in primary human skeletal myocytes. Treatment of myocytes with the Ca2+ ionophore, ionomycin, for 6 h resulted in an increase in both LIF mRNA and LIF protein levels. This finding suggests that Ca2+ may be involved in the regulation of LIF in endurance-exercised skeletal muscle. In conclusion, primary human skeletal myocytes have the capability to produce LIF in response to ionomycin stimulation and LIF mRNA levels increase in skeletal muscle following concentric exercise. The finding that the increase in LIF mRNA levels is not followed by a similar increase in skeletal muscle LIF protein suggests that other exercise stimuli or repetitive stimuli are necessary in order to induce a detectable accumulation of LIF protein.

(Received 13 December 2007; accepted after revision 20 February 2008; first published online 21 February 2008)
Corresponding author B. K. Pedersen: Centre of Inflammation and Metabolism, Rigshospitalet – Section 7641, Tagensvej 20, DK-2100, Copenhagen, Denmark. Email: bkp{at}rh.dk







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