Abstract
IL6 is a myokine expressed by skeletal muscle cells upon exercise; the mechanisms regulating this process are poorly understood. IP3-dependent calcium signals are involved in IL6 expression and IP3-dependent signals are mediated by extra-cellular ATP. IL6 has both positive and negative loops regulating its expression through activation of negative regulators as SOCS in processes mediated by STAT3. Rat myotubes were electrically stimulated (ES, 45 Hz, 400 pulses) and expression of both IL6 and SOCS3 was followed by RT-PCR. SOCS3 and pSTAT3 levels were detected by immunoblot. ELISA allowed detection of IL6 in culture medium. ES increased both early IL6 expression and late pSTAT3 levels in a process inhibited by blockers of purinergic receptors. IL6 was secreted from ATP-stimulated cells and exogenous IL6 increased pSTAT3 levels through JAK2 kinase. STAT3 in turn had an effect on the expression of both IL6 and SOCS3. ATP increased IL6 mRNA with an EC50 of 3–5 μM. 100 μM. ADP stimulated IL6 but neither UDP nor UTP (up to 500 μM) did increase IL6 expression. Expression of IL6 in skeletal muscle cells is a process regulated by extra cellular ATP and P2Y receptors as is STAT3 phosphorylation. Activation of STAT3 occurs via an indirect mechanism that includes both increase in expression and release of IL6. IL6 fosters both its own expression and the expression of SOCS3. FONDAP 15010006, FONDECYT 1080120
Published Version
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