Effects of concentric and eccentric muscle contractions on IL-6 signaling in human skeletal muscle and downstream regulation of HSP-72 gene expression : Is IL-6 signaling involved in exercise-induced cytoprotection?




Harvey, Travis.

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Purpose: To determine the effects of concentric and eccentric muscle contractions on IL-6 signaling and its possible downstream regulation of HSP-72 expression in human skeletal muscle, and whether contraction-induced IL-6 expression may initiate a cytoprotective mechanism in the muscle by activating HSP-72 and HSP-27. Methods: Using a cross-over design, 10 recreationally active males (20.60 ± 2.80 yrs; 77.35 ± 12.79 kg) participated in 2 separate bouts of 10 sets of 10 unilateral isokinetic knee extensions at 30°/sec. Each subject performed one concentric (CON) and one eccentric (ECC) bout, with strength assessed 5 days prior to and at 24 and 48 hr after the bout. Muscle soreness and blood samples were sampled immediately before exercise (PRE), immediately post-exercise (POST), and at 2, 6, 24, and 48 hr after exercise for serum levels of CK, IL-6, IL-1β, and TNF-α. Muscle biopsies were obtained at PRE, POST, and at 2 and 6 hr post-exercise and assessed for protein levels of IL-6, HSP-72, HSP-27, NF-кB, p38 MAPK, STAT-1, and STAT-3 and for mRNA expression of IL-6, HSP-72, and HSP-27. Repeated measures MANOVA for isokinetic peak torque revealed a significant decrease in strength at 24 and 48 hr post-exercise. Repeated measures MANOVA on muscle soreness and CK located a significant (p ≤ 0.05) main effect for time for both variables, but not for contraction type. Repeated measures MANOVA for cytokine serum variables demonstrated no significant results. Repeated measures MANOVA for muscle variables demonstrated no significant main effect for contraction, though a significant main effect for time was located. Pairwise comparisons demonstrated a significant difference from immediately post-exercise to 6 hr post-exercise for HSP-27. Gene expression of muscle variables demonstrated no significant results. Conclusion: The CON and ECC bouts demonstrated muscle damage through significant elevations in CK and muscle fatigue through significantly decreased torque production at 24 and 48 hr post-exercise. However, the damage induced during the acute bouts appears to have been insufficient to produce systemic and intramuscular signaling of the IL-6 pathway and its associated factors. Further human research still needs to be conducted on this pathway with the factors investigated here, though other exercise intensities and modes should be considered.


Includes bibliographical references (p. 131-148).


Musculoskeletal system -- Physiology., Muscle contraction., Isokinetic exercise -- Physiological aspects., Genetic regulation., Interleukin-6., Heat shock proteins., Cellular signal transduction.