Differential expression of the IL-1 system components during in vitro myogenesis: Implication of IL-1 beta in induction of myogenic cell apoptosis

We evaluated the expression of IL-1 system by normal human myogenic cells d uring in vitro myogenesis and the effect of exogenous IL-1 beta. Expression of IL-1 alpha and beta, IL-1 receptor antagonist (IL-1Ra), IL-1RI and II, IL-IR accessory protein (1RAcP) and IL-1 beta converting enzyme (ICE) was s tudied by immunocytochemistry, immunoblotting, ELISA and RT-PCR. Cell proli feration was evaluated by [H-3]thymidine incorporation, cell fusion by flow cytometry and cell death by in situ end-labelling, Human normal myogenic c ells constitutively produced IL-1 beta and ICE, with a maximum expression a t time of cell fusion. IL-1Rs and IL-1RAcP expression reached a peak at tim e of commitment to fusion. Myogenic cells produced small amounts of IL-1Ra at, latest stages of culture, and only the intracellular isoform, Exposure of cultures to exogenous IL-1 beta(1-5 ng/ml) induced myogenic cell apoptos is, without effect on cell proliferation or fusion, I beta-induced cell dea th was associated with morphological changes including spreading appearance of cells and alteration of cell alignment. We conclude that (1) human myog enic cells constitutively produce IL-1 beta; (2) IL-1 system components are differentially expressed during in vitro myogenesis; (3) IL-1 system parti cipates to the coordinated regulation of cell density during normal myogene sis, which could serve to control the muscle mass in vivo.