Interferon‐mediated inhibition of differentiation in a murine myoblast cell line

Abstract

The effects of highly purified (greater than 5 X 10(7) IU/mg) murine beta-interferon (IFN) on a mouse myoblast line (MM14DZ) have been investigated to confirm and extend the previous observation that partially purified chicken interferon inhibits differentiation of cultured avian myoblasts (Lough et al., Biochem Biophys Res Commun 109:92, 1982). Cultures treated with 20-2,000 lU IFN/ml medium for 5 days exhibited dose-dependent 1) inhibition of differentiation, as indicated by reduced myotube formation and creatine kinase (CK) activity and 2) increases in DNA content, suggesting that the inhibitory effect was accompanied by continued proliferation of myoblasts. Mock-IFN had no such effects. Based on findings in other systems that IFN inhibits activity of ornithine decarboxylase (ODC), the polyamine products of which are required for myogenesis, the hypothesis that inhibition of differentiation was mediated by an effect of IFN on polyamine metabolism was tested. However, observations that 1) IFN-treated myoblasts retained control levels of ODC activity and 2) exogenous polyamines did not prevent IFN-inhibition did not indicate such a mechanism of action. On the other hand, treatment of control cultures with polyamines alone resulted in potentiation of myogenesis as revealed by precocious myotube formation and a marked increase in CK activity.

Differentiation in C2C12 myoblasts depends on the expression of endogenous IGFs and not serum depletion

“…A depletion of serum from myoblast cultures has been considered to be essential for terminal differentiation, because serum mitogens generally inhibit differentiation and/or stimulate proliferation (4,11,22,25,26,30,33,36,38,50,57,61). In addition to bFGF and TGF-␤, interferon-␤ (36), platelet-derived growth factor-BB (26,57), acidic FGF (30,38), leukemia inhibitory factor, TGF-␣, interleukin-6 (4), keratinocyte FGF (38), tumor necrosis factor (50), and hepatocyte growth factor (22) have been shown to inhibit differentiation and/or stimulate proliferation.…”

“…myoblasts; insulin-like growth factor I; insulin-like growth factor II; serum mitogens; differentiation PROLIFERATION AND DIFFERENTIATION in myoblast cultures are subject to control by serum mitogens, as demonstrated by effects of medium conditioning or mitogen addition or removal. The majority of serum mitogens are considered to act as an inhibitor of myogenic differentiation via, at least in part, the downregulation of myogenic determination factors (4,11,22,26,30,36,38,50,57). The most extensively studied mitogenic and/or myogenic factors are basic fibroblast growth factor (bFGF), transforming growth factor (TGF)-␤, and insulin-like growth factors (IGFs; see Ref.…”

The 2′-5′ Oligoadenylate/RNase L/RNase L Inhibitor Pathway Regulates Both MyoD mRNA Stability and Muscle Cell Differentiation

“…The activation of these proteins seems to be sequential and may explain why previous studies, assessing the role of IFN during differentiation, appear to be conflicting. Some studies describe an inhibitory effect of IFN on myogenesis (26,31), whereas others report a positive effect (1,13,44).…”

Hormonal control of muscle growth

“…The correlation between mitogenicity and inhibition of differentiation is poor if consideration is given to any purified proteins other than FGF, such as TGF-beta (see below) and interferon. 144 Although FGF does not inhibit differentiation in L6 myoblasts,52 its effects are not restricted to the mouse lines studied by Olwin and Hauschka. '"7 Glaser and his colleagues' 1 7 .…”