dc.creatorBustamante, Mario
dc.creatorFernández Verdejo, Rodrigo
dc.creatorJaimovich Pérez, Enrique
dc.creatorBuvinic Radic, Sonja
dc.date.accessioned2014-12-24T01:20:04Z
dc.date.available2014-12-24T01:20:04Z
dc.date.created2014-12-24T01:20:04Z
dc.date.issued2014
dc.identifierAm J Physiol Endocrinol Metab 306: E869–E882, 2014.
dc.identifierhttps://repositorio.uchile.cl/handle/2250/129482
dc.description.abstractS. Electrical stimulation induces IL-6 in skeletal muscle through extracellular ATP by activating Ca2 signals and an IL-6 autocrine loop. Am J Physiol Endocrinol Metab 306: E869 –E882, 2014. First published February 11, 2014; doi:10.1152/ajpendo.00450.2013.— Interleukin-6 (IL-6) is an important myokine that is highly expressed in skeletal muscle cells upon exercise. We assessed IL-6 expression in response to electrical stimulation (ES) or extracellular ATP as a known mediator of the excitation-transcription mechanism in skeletal muscle. We examined whether the canonical signaling cascade downstream of IL-6 (IL-6/JAK2/STAT3) also responds to muscle cell excitation, concluding that IL-6 influences its own expression through a positive loop. Either ES or exogenous ATP (100 M) increased both IL-6 expression and p-STAT3 levels in rat myotubes, a process inhibited by 100 M suramin and 2 U/ml apyrase. ATP also evoked IL-6 expression in both isolated skeletal fibers and extracts derived from whole FDB muscles. ATP increased IL-6 release up to 10-fold. STAT3 activation evoked by ATP was abolished by the JAK2 inhibitor HBC. Blockade of secreted IL-6 with a neutralizing antibody or preincubation with the STAT3 inhibitor VIII reduced STAT3 activation evoked by extracellular ATP by 70%. Inhibitor VIII also reduced by 70% IL-6 expression evoked by ATP, suggesting a positive IL-6 loop. In addition, ATP increased up to 60% the protein levels of SOCS3, a negative regulator of the IL-6 signaling pathway. On the other hand, intracellular calcium chelation or blockade of IP3-dependent calcium signals abolished STAT3 phosphorylation evoked by either extracellular ATP or ES. These results suggest that expression of IL-6 in stimulated skeletal muscle cells is mediated by extracellular ATP and nucleotide receptors, involving IP3-dependent calcium signals as an early step that triggers a positive IL-6 autocrine loop.
dc.languageen
dc.publisherAmerican Physiological Society
dc.rightshttp://creativecommons.org/licenses/by-nc-nd/3.0/cl/
dc.rightsAttribution-NonCommercial-NoDerivs 3.0 Chile
dc.subjectMyokines
dc.titleElectrical stimulation induces IL-6 in skeletal muscle through extracellular ATP by activating Ca2 signals and an IL-6 autocrine loop
dc.typeArtículo de revista


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