title: Growth factor and cytokine interactions in myogenesis. Part I. The effect of TNF-alpha and IFN-gamma on IGF-I-dependent differentiation in mouse C2C12 myogenic cells.
abstract: The aim of this study was to examine the potential interactions of IGF-I with TNF-alpha and IFN-gamma with regard to regulation of the myogenesis and proliferative potential of mouse C2C12 myoblasts. The stimulation of myogenesis by IGF-I (30 nmol/l) was manifested by an enhanced myoblast fusion and expression of myosin heavy chain (MHC) during the first 3 days of differentiation. IGF-I-dependent fusion and MHC expression was reduced by TNF-alpha and IFN-gamma. Both cytokines prevented the stimulatory effect of IGF-I on MyoD expression with minor modification of the myogenin level. Both TNF-alpha and IFN-gamma activated the expression of cyclin A in myoblasts restimulated to proliferation; however, when used in combination with IGF-I these cytokines prevented the rise in cyclin A induced by growth factor.
  
  
  CONCLUSIONS
  i) TNF-alpha and IFN-gamma reduce IGF-I-dependent myogenesis which was manifested by the reduction of myoblast fusion and MHC cellular levels, ii) Molecular mechanisms of inhibitory action of TNF-alpha and IFN-gamma on IGF-I-mediated differentiation involve a decrease in MyoD whereas myogenin level plays a minor role, iii) TNF-alpha and IFN-gamma increase the proliferative potential of myoblasts; however, they reduced the mitogenic effect of IGF-I, manifested by a decrease of IGF-I-stimulated cyclin A expression in myoblasts reinduced to proliferation. Interactions among IGF-I and proinflammatory cytokines are therefore important to establish a number of myoblasts and the onset of myogenesis during muscle regeneration.
authors.affiliation: Department of Physiological Sciences, Faculty of Veterinary Medicine, Warsaw University of Life Sciences (SGGW), Nowoursynowska 159, 02-776 Warsaw, Poland.
authors.forename: W
authors.initials: W
authors.lastname: Wieteska-Skrzeczyńska
authors.forename: K
authors.initials: K
authors.lastname: Grzelkowska-Kowalczyk
authors.forename: J
authors.initials: J
authors.lastname: Tokarska
authors.forename: K
authors.initials: K
authors.lastname: Grabiec
mesh_terms: D000818:Animals; D002460:Cell Line; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D007371:Interferon-gamma / Q000494:pharmacology*; D051379:Mice; D018482:Muscle, Skeletal / Q000166:cytology / Q000254:growth & development; D032446:Myoblasts / Q000187:drug effects*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: D014409:Tumor Necrosis Factor-alpha; D007334:Insulin-Like Growth Factor I; D007371:Interferon-gamma