Calprotectin is released from human skeletal muscle tissue during exercise.
Skeletal muscle has been identified as a secretory organ. We hypothesized that IL-6, a cytokine secreted from skeletal muscle during exercise, could induce production of other secreted factors in skeletal muscle. IL-6 was infused for 3 h into healthy young males (n = 7) and muscle biopsies obtained at time points 0, 3 and 6 h in these individuals and in resting controls. Affymetrix microarray analysis of gene expression changes in skeletal muscle biopsies identified a small set of genes changed by IL-6 infusion. RT-PCR validation confirmed that S100A8 and S100A9 mRNA were up-regulated 3-fold in skeletal muscle following IL-6 infusion compared to controls. Furthermore, S100A8 and S100A9 mRNA levels were up-regulated 5-fold in human skeletal muscle following cycle ergometer exercise for 3 h at approximately 60% of in young healthy males (n = 8). S100A8 and S100A9 form calprotectin, which is known as an acute phase reactant. Plasma calprotectin increased 5-fold following acute cycle ergometer exercise in humans, but not following IL-6 infusion. To identify the source of calprotectin, healthy males (n = 7) performed two-legged dynamic knee extensor exercise for 3 h with a work load of approximately 50% of peak power output and arterial-femoral venous differences were obtained. Arterial plasma concentrations for calprotectin increased 2-fold compared to rest and there was a net release of calprotectin from the working muscle. In conclusion, IL-6 infusion and muscle contractions induce expression of S100A8 and S100A9 in skeletal muscle. However, IL-6 alone is not a sufficient stimulus to facilitate release of calprotectin from skeletal muscle.
Centre of Inflammation and Metabolism at Department of Infectious, Diseases and Copenhagen Muscle Research Centre, Rigshospitalet, University of Copenhagen, Denmark.
Ole Hartvig
OH
Mortensen
Kasper
K
Andersen
Christian
C
Fischer
Anders Rinnov
AR
Nielsen
Søren
S
Nielsen
Thorbjörn
T
Akerström
Maj-brit
MB
Aastrøm
Rehannah
R
Borup
Bente Klarlund
BK
Pedersen
D000328:Adult; D001706:Biopsy; D015444:Exercise / Q000502:physiology*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D015850:Interleukin-6 / Q000008:administration & dosage / Q000494:pharmacology*; D039841:Leukocyte L1 Antigen Complex / Q000235:genetics / Q000378:metabolism*; D008297:Male; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
D015850:Interleukin-6; D039841:Leukocyte L1 Antigen Complex; D009124:Muscle Proteins; D012333:RNA, Messenger