title: Exercise induces interleukin-8 receptor (CXCR2) expression in human skeletal muscle.
abstract: Exercise induces a marked increase in interleukin-8 (IL-8) mRNA and protein expression within skeletal muscle fibres. Interleukin-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 maximum oxygen uptake (n = 8) or rest (n = 7). Muscle biopsy samples were obtained from the vastus lateralis before exercise (0 h), immediately after exercise (3 h), and at 4.5, 6, 9 and 24 h. Skeletal muscle CXCR2 mRNA increased significantly in response to exercise (3 and 4.5 h) when compared with pre-exercise samples. Expression of the CXCR2 protein was low in skeletal muscle biopsies before exercise and at the end of the exercise period (3 h). However, at 4.5-9 h, an increase in CXCR2 protein was seen in the vascular endothelium, and also slightly 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.
authors.affiliation: Centre of Inflammation and Metabolism, Rigshospitalet - Section 7641, Blegdamsvej 9, DK-2100, Copenhagen, Denmark.
authors.forename: Lone
authors.initials: L
authors.lastname: Frydelund-Larsen
authors.forename: Milena
authors.initials: M
authors.lastname: Penkowa
authors.forename: Thorbjorn
authors.initials: T
authors.lastname: Akerstrom
authors.forename: Alaa
authors.initials: A
authors.lastname: Zankari
authors.forename: Søren
authors.initials: S
authors.lastname: Nielsen
authors.forename: Bente Klarlund
authors.initials: BK
authors.lastname: Pedersen
mesh_terms: D000328:Adult; D015703:Antigens, CD / Q000378:metabolism; D000071063:Endoglin; D004730:Endothelium, Vascular / Q000378:metabolism; D015444:Exercise / Q000502:physiology*; D005455:Fluorescent Antibody Technique; D006801:Humans; D008297:Male; D018485:Muscle Fibers, Skeletal / Q000378:metabolism; D018482:Muscle, Skeletal / Q000098:blood supply / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism; D023063:Receptors, Interleukin-8B / Q000378:metabolism*; D012016:Reference Values; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D015854:Up-Regulation
chemical_list: D015703:Antigens, CD; C064206:ENG protein, human; D000071063:Endoglin; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D023063:Receptors, Interleukin-8B