Adenosine A2B Receptors - Mediated Induction of Interleukin-6 in Skeletal Muscle Cells.

OBJECTIVES

Inflammatory response and cytokine activation are markedly stimulated in skeletal muscle during various conditions. Interleukin-6 (IL-6), a pro-inflammatory cytokine, has pleiotropic effects on skeletal muscle. Adenosine, released by all cell types, binds to a class of G protein-coupled receptors to induce various skeletal muscle effects. The aim of this work was to investigate whether activation of adenosine receptors, particularly adenosine A2B receptors, could stimulate IL-6 gene expression in rat L6 skeletal muscle cells.

MATERIALS AND METHODS

The rat L6 skeletal muscle cells were cultured in 25 cm flasks. These differentiated cells were treated and then quantitative reverse transcription-polymerase chain reaction (Probe-based) was used to analyze IL-6 gene expression level among different treatment conditions.

RESULTS

Adenosine-5'--ethyluronamide (NECA), a stable adenosine analogue, concentration- and time-dependently stimulates IL-6 gene expression in skeletal muscle cells. The effect of NECA is inhibited by a selective adenosine A2B receptor antagonist, PSB 603. By using cyclic adenosine monophosphate (cAMP)-arising reagent forskolin, cAMP is found to be involved in the up-regulation of IL-6 induction.

CONCLUSION

Here, a novel relationship between adenosine and IL-6 up-regulation has been demonstrated for the first time; IL-6 up-regulation induced by NECA is mediated by adenosine A2B receptor activation in skeletal muscle and is dependent on mainly a cAMP pathway. Adenosine A2B receptors are, thus, potentially important pharmacological targets in treating inflammation and related diseases in skeletal muscle tissues.