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This Article Full Text Full Text (PDF) All Versions of this Article: 290/5/C1428    most recent 00449.2005v1 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 PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (4) Citing Articles via Google Scholar Google Scholar Articles by Juretic, N. Articles by Riveros, N. Search for Related Content PubMed PubMed Citation Articles by Juretic, N. Articles by Riveros, N.

MUSCLE CELL BIOLOGY AND CELL MOTILITY

Depolarization-induced slow Ca²⁺ transients stimulate transcription of IL-6 gene in skeletal muscle cells

Nevenka Jureti, Paola García-Huidobro, Juan Antonio Iturrieta, Enrique Jaimovich, and Nora Riveros

Centro de Estudios Moleculares de la Célula, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Santiago, Chile

Submitted 6 September 2005 ; accepted in final form 22 December 2005

Contracting skeletal muscle produces and releases interleukin-6 (IL-6) in high amounts. Nevertheless, the mechanisms underlying IL-6 expression are not understood. Because inositol-1,4,5-trisphosphate (IP₃)-mediated slow Ca²⁺ signals evoked by depolarization of skeletal myotubes appears to play a role in the regulation of gene expression, we examined its involvement on IL-6 transcription. With the use of semiquantitative RT-PCR, we have shown that K⁺ depolarization of myotubes induces a transient increase in IL-6 mRNA level, which peaks at 3–4 h and is independent of extracellular Ca²⁺. Inhibitors of IP₃-dependent Ca²⁺ signals, like 2-aminoethoxydiphenyl borate (2-APB) and U-73122, decreased activation of IL-6 gene expression as did Ca²⁺ signals inhibitor BAPTA-AM, whereas ryanodine, a fast Ca²⁺ transient inhibitor, had no effect on IL-6 induction. Depolarization of myotubes transiently transfected with a reporter gene construct, containing 651 bp of IL-6 promoter, induced a twofold increase in promoter activity, which was abolished by either 2-APB or U-73122 and remained unaffected after ryanodine treatment. Site-directed mutagenesis of parental construct allowed us to identify activator protein-1 and NF-B sequences as regulatory elements involved in IL-6 upregulation. Our results provide evidence for involvement of IP₃-mediated Ca²⁺ signals on IL-6 transcription in skeletal muscle cells.

myotubes; membrane potential; intracellular Ca²; cytokines; gene expression

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