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This Article Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: 297/4/E866    most recent 00104.2009v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Nedachi, T. Articles by Kanzaki, M. PubMed PubMed Citation Articles by Nedachi, T. Articles by Kanzaki, M.

Characterization of contraction-inducible CXC chemokines and their roles in C₂C₁₂ myocytes

¹Center for Research Strategy and Support (CRESS), ²Division of Biomaterials, Biomedical Engineering Research Organization, and ³Graduate School of Biomedical Engineering, Tohoku University, and ⁴Japan Science and Technology Agency, Core Research for Evolutionary Science and Technology, Sendai, Japan

Submitted 17 February 2009 ; accepted in final form 18 July 2009

Physical exercise triggers the release of several cytokines/chemokines from working skeletal muscles, but the underlying mechanism(s) by which skeletal muscles decipher and respond to highly complex contractile stimuli remains largely unknown. In an effort to investigate the regulatory mechanisms of the expressions of two contraction-inducible CXC chemokines, CXCL1/KC and CXCL5/LIX, in contracting skeletal muscle cells, we took advantage of our in vitro exercise model using highly developed contractile C₂C₁₂ myotubes, which acquire properties similar to those of in vivo skeletal muscle via manipulation of Ca²⁺ transients with electric pulse stimulation (EPS). Production of these CXC chemokines was immediately augmented by EPS-evoked contractile activity in a manner dependent on the activities of JNK and NF-B, but not p38, ERK1/2, or calcineurin. Intriguingly, exposure of myotubes to cyclic mechanical stretch also induced expression of these CXC chemokines; however, a much longer period of stimulation (12 h) was required, despite rapid JNK phosphorylation. We also demonstrate herein that CXCL1/KC and CXCL5/LIX have the ability to raise intracellular Ca²⁺ concentrations via CXCR2-mediated activation of pertussis toxin-sensitive G_i proteins in C₂C₁₂ myoblasts, an action at least partially responsible for their migration and differentiation. Although we revealed a possible negative feedback regulation of their own production in response to the contractile activity in differentiated myotubes, exogenous administration of these CXC chemokines did not acutely influence either insulin-induced Akt phosphorylation or GLUT4 translocation in C₂C₁₂ myotubes. Taken together, these data shed light on the fundamental characteristics of contraction-inducible CXC chemokine production and their potential roles in skeletal muscle cells.

chemokine; exercise; glucose transporter 4; muscle