Exercise-induced liver chemokine CXCL-1 expression is linked to muscle-derived interleukin-6 expression

Line Pedersen, Henriette Pilegaard, Jakob Hansen, Claus Brandt, Helle Adser, Juan Hidalgo, Jesper Olesen, Bente Klarlund Pedersen, Pernille Hojman

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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 in mice. 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. © 2011 The Authors. Journal compilation © 2011 The Physiological Society.
Original languageEnglish
Pages (from-to)1409-1420
JournalJournal of Physiology
Volume589
DOIs
Publication statusPublished - 1 Mar 2011

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    Pedersen, L., Pilegaard, H., Hansen, J., Brandt, C., Adser, H., Hidalgo, J., Olesen, J., Pedersen, B. K., & Hojman, P. (2011). Exercise-induced liver chemokine CXCL-1 expression is linked to muscle-derived interleukin-6 expression. Journal of Physiology, 589, 1409-1420. https://doi.org/10.1113/jphysiol.2010.200733