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

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Abstract
We evaluated the expression of IL-1 system by normal human myogenic cells during in vitro myogenesis and the effect of exogenous IL-1β. Expression of IL-1α and β, IL-1 receptor antagonist (IL-1Ra), IL-1RI and II, IL-1R accessory protein (IL-1RAcP) and IL-1β converting enzyme (ICE) was studied by immunocytochemistry, immunoblotting, ELISA and RT–PCR. Cell proliferation was evaluated by [3H]thymidine incorporation, cell fusion by flow cytometry and cell death by in situ end-labelling. Human normal myogenic cells constitutively produced IL-1β and ICE, with a maximum expression at time of cell fusion. IL-1Rs and IL-1RAcP expression reached a peak at time 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-1β (1–5 ng/ml) induced myogenic cell apoptosis, without effect on cell proliferation or fusion. IL-1β-induced cell death was associated with morphological changes including spreading appearance of cells and alteration of cell alignment. We conclude that (1) human myogenic cells constitutively produce IL-1β; (2) IL-1 system components are differentially expressed during in vitro myogenesis; (3) IL-1 system participates to the coordinated regulation of cell density during normal myogenesis, which could serve to control the muscle mass in vivo.

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