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  • High dexamethasone concentration prevents stimulatory effects of TNF-alpha and LPS on IL-6 secretion from the precursors of human muscle regeneration
    Prelovšek, Oja ...
    A frequent finding in patients surviving critical illness myopathy is chronic muscle dysfunction. Its pathogenesis is mostly unknown; one explanation could be that muscle regeneration, which normally ... follows myopathy, is insufficient in these patients because of a high glucocorticoid level in their blood. Glucocorticoids can prevent stimulatory effects of proinflammatory factors on the interleukin (IL)-6 secretion, diminishing in this way the autocrine and paracrine IL-6 actions known to stimulate proliferation at the earliest, myoblast stage of muscle formation. To test this hypothesis, we compared the effects of major proinflammatory agents štumor necrosis factor (TNF)-alpha andendotoxin lipopolysaccharide (LPS)đ on the IL-6 secretion from the muscle precursors and then studied the influence of dexamethasone (Dex) on these effects. Mononuclear myoblasts, which still proliferate, were compared with myotubes in which this capacity is already lost. For correct interpretation ofresults, cultures were examined for putative apoptosis and necrosis. We found that constitutive secretion of IL-6 did not differ significantly betweenmyoblasts and myotubes; however, the TNF-alpha- and LPS-stimulated IL-6release was more pronounced (P < 0.001) in myoblasts. Dex, applied at the 0.1-100 nM concentration range, prevented constitutive and TNF-alpha- and LPS-stimulated IL-6 release at both developmental stages but only at high concentration (P < 0.01). Although there are still missing links to it, our results support the concept that high concentrations of glucocorticoids, met in critically ill patients, prevent TNF-alpha- and LPS-stimulated IL-6 secretion. This results in reduced IL-6-mediated myoblast proliferation, leading to the reduced final mass of the regenerated muscle.
    Vir: American journal of physiology. regulatory, integrative and comparative physiology. - ISSN 0363-6119 (Letn. 291, št. 6, 2006, str. R1651-R1656)
    Vrsta gradiva - članek, sestavni del
    Leto - 2006
    Jezik - angleški
    COBISS.SI-ID - 22260185

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