title: Exercise-induced liver chemokine CXCL-1 expression is linked to muscle-derived interleukin-6 expression.
abstract: The chemokine CXC ligand-1 (CXCL-1) is a small cytokine that elicits effects by signalling through the chemokine receptor CXCR2. CXCL-1 has neutrophil chemoattractant activity, is involved in the processes of angiogenesis, inflammation and wound healing, and may possess neuroprotective effects. The aim of this study was to unravel the mechanisms whereby CXCL-1 is regulated by exercise inmice. After a single bout of exercise, CXCL-1 protein increased in serum(2.4-fold), and CXCL-1 mRNA in muscle (6.5-fold) and liver (41-fold). These increases in CXCL-1 were preceded by increases in serum interleukin-6 (IL-6) and muscle IL-6 mRNA. In contrast, exercise-induced regulation of liver CXCL-1 mRNA expression was completely blunted in IL-6 knockout mice. Based on these findings, we examined the possible existence of a muscle-to-liver axis by overexpressing IL-6 in muscles. This resulted in increases in serum CXCL-1 (5-fold) and liver CXCL-1 mRNA expression (24-fold) compared with control. Because IL-6 expression and release are known to be augmented during exercise in glycogen-depleted animals, CXCL-1 and IL-6 expression were examined after exercise in overnight-fasted mice.We found that fasting significantly augmented serum CXCL-1, and CXCL-1 expression in liver and muscle. Taken together, these data indicate that liver is the main source of serum CXCL-1 during exercise in mice, and that the CXCL-1 expression in the liver is regulated by muscle-derived IL-6.
authors.affiliation: Centre of Inflammation and Metabolism at Department of Infectious Diseases and Copenhagen Muscle Research Centre, Rigshospitalet and Faculty of Health Sciences, University of Copenhagen, Denmark.
authors.forename: Line
authors.initials: L
authors.lastname: Pedersen
authors.forename: Henriette
authors.initials: H
authors.lastname: Pilegaard
authors.forename: Jakob
authors.initials: J
authors.lastname: Hansen
authors.forename: Claus
authors.initials: C
authors.lastname: Brandt
authors.forename: Helle
authors.initials: H
authors.lastname: Adser
authors.forename: Juan
authors.initials: J
authors.lastname: Hidalgo
authors.forename: Jesper
authors.initials: J
authors.lastname: Olesen
authors.forename: Bente Klarlund
authors.initials: BK
authors.lastname: Pedersen
authors.forename: Pernille
authors.initials: P
authors.lastname: Hojman
mesh_terms: D000818:Animals; D054360:Chemokine CXCL1 / Q000096:biosynthesis*; D018925:Chemokines / Q000096:biosynthesis; D005080:Exercise Test / Q000379:methods; D005215:Fasting / Q000378:metabolism; D005786:Gene Expression Regulation; D015850:Interleukin-6 / Q000096:biosynthesis*; D008099:Liver / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018482:Muscle, Skeletal / Q000378:metabolism*; D010805:Physical Conditioning, Animal / Q000379:methods*; D005082:Physical Exertion / Q000502:physiology*
chemical_list: D054360:Chemokine CXCL1; D018925:Chemokines; C475895:Cxcl1 protein, mouse; D015850:Interleukin-6