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First published online on October 9, 2006.
Experimental Physiology (2006)
DOI: 10.1113/expphysiol.2006.034769
© The Physiological Society 2006

A more recent version of this article appeared on January 1, 2007
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Received July 9, 2006
Revised July 28, 2006
Accepted after revision October 5, 2006


Muscle [260]

Exercise induces interleukin-8 receptor (CXCR2) expression in human skeletal muscle

Lone Frydelund-Larsen 1, Milena Penkowa 2, Thorbjorn Akerstrom 1, Alaa Zankari 1, Soren Nielsen 1, Bente Klarlund Pedersen 1*

1 Centre of Inflammation and Metabolism, Rigshospitalet
2 Section of Neuroprotection, University of Cope

* To whom correspondence should be addressed. E-mail: bkp{at}rh.dk.


   Abstract
Exercise induces a marked increase in interleukin (IL)-8 mRNA and protein expression within skeletal muscle fibres. IL-8 belongs to a subfamily of CXC chemokines containing a Glu-Leu-Arg (ELR) motif. CXC chemokines with ELR motifs are potent angiogenic factors in vivo and IL-8 has been shown to act as an angiogenic factor in human microvascular endothelial cells by binding to the CXC receptor 2 (CXCR2). In the present study, we examined the expression of the interleukin-8 receptor CXCR2 in human skeletal muscle biopsies after concentric exercise. Healthy volunteers were randomized to either 3 h of cycle ergometer exercise at 60% of VO2max (n=8) or rest (n=7). Muscle biopsy samples were obtained from the vastus lateralis prior to exercise (0), immediately after exercise (3 h), and at 4.5, 6, 9, and 24 h. Skeletal muscle CXCR2 mRNA increased significantly in response to exercise (3h and 4.5 h) when compared to pre-exercise samples.. Expression of the CXCR2 protein was low in skeletal muscle biopsies prior to exercise and at the end of the exercise period (3 h). However, at 4.5 h to 9 h, an increase in CXCR2 protein was seen in the vascular endothelium, and also mildly within the muscle fibres, as determined by immunohistochemistry. The present study demonstrates that concentric exercise induces CXCR2 mRNA and protein expression in the vascular endothelial cells of the muscle fibres. These findings suggest that muscle-derived IL-8 may act locally to stimulate angiogenesis through CXCR2 receptor signalling.

Key Words: Angiogenesis, Cytokine, Exercise




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