Calprotectin is released from human skeletal muscle tissue during exercise

• Published in: The Journal of physiology 2008-07, Vol.586 (14), p.3551-3562
• Main Authors: Mortensen, Ole Hartvig, Andersen, Kasper, Fischer, Christian, Nielsen, Anders Rinnov, Nielsen, Søren, Åkerström, Thorbjörn, Aastrøm, Maj‐brit, Borup, Rehannah, Pedersen, Bente Klarlund
• Format: Article
• Language: English
• Subjects: Adult; Biopsy; Exercise - physiology; Gene Expression Profiling; Gene Expression Regulation; Humans; Interleukin-6 - administration & dosage; Interleukin-6 - pharmacology; Leukocyte L1 Antigen Complex - genetics; Leukocyte L1 Antigen Complex - metabolism; Male; Muscle Proteins - genetics; Muscle Proteins - metabolism; Muscle, Skeletal - metabolism; RNA, Messenger - genetics; RNA, Messenger - metabolism; Skeletal Muscle and Exercise
• ISSN: 0022-3751; 1469-7793
• DOI: 10.1113/jphysiol.2008.153551

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 ∼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 ∼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.