Contraction‐induced IL‐6 production in rat soleus muscle is dependent on calcineurin activation

Abstract

During prolonged exercise, skeletal muscles produce and release IL-6. We recently showed in exercised rats that high levels of IL-6 mRNA were associated with high Modulatory Calcineurin-Interacting protein-1 (MCIP-1) mRNA levels, reflecting high calcineurin activity, in both type I and IIa fibers. The present work aimed at determining if this was due to a direct relationship or not. We treated rats with cyclosporine A (CsA) or vehicle (Vhl) and subjected them to treadmill running. Soleus muscles were removed. MCIP-1 and IL-6 mRNA levels were assessed by RT-PCR. Because low carbohydrates availability enhances IL-6 transcription through p38 Mitogen Activated Protein Kinase pathway, muscle glycogen content and glycemia were measured and p38 phosporylation was determined by western blotting. In Vhl group, exercise induced a large increase in IL-6 and MCIP-1 mRNA levels in soleus muscle, and an enhanced p38 phosphorylation. CsA did not affect running time, glycemia or soleus glycogen content. Consistently, despite a tendency to decrease, there was no significant difference in p38 phosphorylation in both exercised and non-exercised groups. In exercised rats, CsA treatment totally inhibited MCIP-1 mRNA increase, and significantly blunted IL-6 gene transcription. Because CsA blocked exercise-induced increase of MCIP-1 transcription without affecting p38 activation, our results provide strong evidence that exercise-induced IL-6 production in slow-type muscle is dependent on calcineurin activation. Support : Délégation Générale pour l'Armement 02 CO 008/II