Proinflammatory Cytokines Regulate Myogenic Cell Proliferation and Fusion but Have No Impact on Myotube Protein Metabolism or Stress Protein Expression

Ji, Shaoquan; Neustrom, S.; Willis, Gawain M.; Spurlock, Michael E.

doi:10.1089/jir.1998.18.879

Cited by 30 publications

(21 citation statements)

References 33 publications

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“…These results are consistent with the involvement of IL-1 in acute-inflammatory-mediated graft cell death after grafting of SkM to muscle (12), proapoptotic effects of IL-1 on SkM in vitro (20), and the inhibitory effect of IL-1 on SkM proliferation (41). Graft loss is a major limitation of cell therapy, and strategies to attenuate environmental stress related to cytokines and free radicals may improve outcome, as we have observed (24,42).…”

Section: Discussionsupporting

confidence: 88%

Transplantation of skeletal myoblasts secreting an IL-1 inhibitor modulates adverse remodeling in infarcted murine myocardium

Murtuza

Suzuki

Bou‐Gharios

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

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After myocardial infarction (MI), adverse remodeling with left ventricular (LV) dilatation is a major determinant of poor outcome. Skeletal myoblast (SkM) implantation improves cardiac function post-MI, although the mechanism is unclear. IL-1 influences post-MI hypertrophy and collagen turnover and is implicated in SkM death after grafting. We hypothesized that SkM expressing secretory IL-1 receptor antagonist (sIL-1ra) at MI border zones would specifically attenuate adverse remodeling and exhibit improved graft cell number. Stable murine male SkM lines (5 ؋ 10 5 cells), expressing or nonexpressing (cont) for sIL-1ra, were implanted into infarct border zones of female nude mice immediately after left coronary artery occlusion. LV ejection fraction (LVEF), end-diastolic diameter, and transmitral peak early͞late (E͞A) flow velocity ratio were determined by echocardiography. Cardiac myocyte hypertrophy and fibrosis were assessed by morphometry, picrosirius red staining, and hydroxyproline assay. At 3 weeks, cont-SkM-engrafted hearts showed reduced hypertrophy, improved LVEF (55.7 ؎ 1.2% vs. MI-only: 40.3 ؎ 2.9%), and preserved E͞A ratios. sIL-1ra-SkM implantation enhanced these effects (LVEF, 67.0 ؎ 2.3%) and significantly attenuated LV dilatation (LV end-diastolic diameter, 4.0 ؎ 1.1 mm vs. cont-SkM, 4.5 ؎ 1.2 mm vs. MI-only, 4.8 ؎ 1.8 mm); this was associated with greater graft numbers, as shown by PCR for male-specific smcy gene. Enzyme zymography showed attenuated matrix metalloproteinase-2 and -9 up-regulation post-MI by either donor SkM type, although infarct-remote zone collagen was reduced only with sIL-1ra-SkM. These results suggest that SkM implantation improves cardiac function post-MI by modulation of adverse remodeling, and that this effect can be significantly enhanced by targeting IL-1 as a key upstream regulator of both adverse remodeling and graft cell death.

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Section: Discussionsupporting

confidence: 88%

Transplantation of skeletal myoblasts secreting an IL-1 inhibitor modulates adverse remodeling in infarcted murine myocardium

Murtuza

Suzuki

Bou‐Gharios

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

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“…The greater intensity and wider distribution of staining observed in the present study may be due to the relatively high antibody concentrations used (1:400 present study; 1:500 DeBleecker; 1:1000 Tews) on paraffin (rather than frozen) sections, and the acute nature of the experimental injuries. Necrotic muscle sarcoplasm stained particularly strongly for TNF-␣, supporting the reported role of TNF-␣ in the induction of muscle proteolysis (Goodman 1991;Zamir et al 1992;Cassatella 1995;Argiles et al 1998), although this may be an indirect effect mediated by glucocorticoids (Ji et al 1998). Muscle atrophy has also been implicated as a trigger for cytokine expression by muscle fibers (Tews and Goebel 1996), and expression of TNF-␣ was also seen in the present study in atrophic muscle fibers at 4 weeks after denervation.…”

Section: Immunostaining Of Normal and Regenerating Musclesupporting

confidence: 88%

“…IL-1, like TNF-␣, is a primary mediator of the inflammatory response (Schindler and Dinarello 1990;Fiers 1991) and is a strong candidate for potential upregulation in the absence of TNF-␣. IL-1 is also likely to be important in muscle regeneration because of its roles in angiogenesis, fibroblast proliferation, and chemotaxis (Schindler and Dinarello 1990;Heckmann et al 1993;Tidball 1995) and, like TNF-␣, its direct effects on proliferation and fusion of myoblasts (Ji et al 1998). …”

Section: Cytokine Interactionsmentioning

confidence: 99%

“…In tissue culture, TNF-␣ enhanced myoblast proliferation and inhibited differentiation and fusion of mouse C2 cells (Szalay and Duda 1997), whereas TNF-␣ inhibited both proliferation and fusion of rat L8 myoblasts (Ji et al 1998). There is strong evidence that TNF-␣ induces muscle proteolysis and is involved in (cachexia) muscle wasting (Goodman 1991;Zamir et al 1992;Cassatella 1995;Argiles et al 1998;Ji et al 1998). TNF-␣ has also been implicated in a number of non-muscle inflammatory diseases, including rheumatoid arthritis (Douni et al 1996), inflammatory bowel disease (Noguchi et al 1998), and multiple sclerosis (Sharief and Hentges 1991).…”

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confidence: 99%

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The Role of Tumor Necrosis Factor-alpha (TNF-α) in Skeletal Muscle Regeneration

Collins

Grounds²

2001

J Histochem Cytochem.

144

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The role of tumor necrosis factor-alpha (TNF-α), an important mediator of the inflammatory response after injury, was investigated in regenerating skeletal muscle. The pattern of expression of TNF-α during muscle regeneration was examined by immunohistochemistry in tissue sections of crush-injured or transplanted muscle autografts and in primary cultures of adult skeletal muscle. TNF-α was highly expressed in injured myofibers, inflammatory cells, endothelial cells, fibroblasts, and mast cells. Myoblasts and myotubes also expressed TNF-α in primary muscle cultures and tissue sections. The essential role of TNF-α and its homologue lymphotoxin-alpha (LT-α) during muscle regeneration was assessed by basic histology in TNF-α(–) and TNF-α(-/-)/LT-α(-/-) mice. No difference was apparent in the onset or pattern of muscle regeneration (i.e., inflammatory response, activation and fusion of myoblasts) between the two strains of null mice or between nulls and normal control mice. However, both strains of null mice appeared more prone to bystander damage of host muscle and regeneration distant from the site of injury/transplantation. Although expression of TNF-α may play an important role in muscle regeneration, the studies in the null mice show that redundancy within the cytokine system (or some other response) can effectively compensate for the absence of TNF-α in vivo. (J Histochem Cytochem 49:989–1001, 2001)

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“…IL-1␤, at concentrations ranging from 1 to 100 ng/ml, has been reported to act on muscle cells cultured in fetal bovine or horse sera by blocking development to a more mature phenotype (10,31), but the mechanism remains unknown. Because activation of the IGF-I receptor is required for differentiation of myoblasts (22), we hypothesized that IL-1␤ acts by inhibiting the ability of IGF-I to promote differentiation of precursors into more mature myotubes.…”

Section: Il-1␤ Blocks Igf-i-dependent Differentiationmentioning

confidence: 99%

IL-1β Impairs Insulin-Like Growth Factor I-Induced Differentiation and Downstream Activation Signals of the Insulin-Like Growth Factor I Receptor in Myoblasts

Broussard¹,

McCusker²,

Novakofski

et al. 2004

The Journal of Immunology

104

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Proinflammatory cytokines are elevated in disorders characterized by muscle wasting and weakness, such as inflammatory myopathies and AIDS wasting. We recently demonstrated that TNF-α impairs the ability of insulin-like growth factor (IGF)-I to promote protein synthesis in muscle precursor cells. In this study we extend these findings by showing that low concentrations of IL-1β impair IGF-I-dependent differentiation of myoblasts, as assessed by expression of the muscle specific protein, myosin heavy chain. In the absence of exogenous IGF-I, IL-1β (1 ng/ml) did not impair muscle cell development. However, in the presence of IGF-I, 100-fold lower concentrations of IL-1β (0.01 ng/ml) significantly suppressed myoblast differentiation, protein synthesis, and myogenin expression. Increasing IL-1β to 1 ng/ml completely blocked the anabolic actions of IGF-I in murine C2C12 myoblasts. Similarly, IL-1β inhibited IGF-I-stimulated protein synthesis in primary porcine myoblasts. IL-1β impaired the actions of IGF-I at a point distal to the IGF receptor, and this was not due to IL-1β-induced cell death. Instead, IL-1β inhibited the ability of IGF-I to phosphorylate tyrosine residues on both of its downstream docking proteins, insulin receptor substrate 1 and insulin receptor substrate 2. These data establish that physiological concentrations of IL-1β block the ability of IGF-I to promote protein synthesis, leading to reduced expression of the myogenic transcription factor, myogenin, and the subsequent development of more mature differentiated cells that express myosin heavy chain. Collectively, the results are consistent with the notion that very low concentrations of IL-1β significantly impair myogenesis, but they are unable to do so in the absence of the growth factor IGF-I.

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Proinflammatory Cytokines Regulate Myogenic Cell Proliferation and Fusion but Have No Impact on Myotube Protein Metabolism or Stress Protein Expression

Cited by 30 publications

References 33 publications

Transplantation of skeletal myoblasts secreting an IL-1 inhibitor modulates adverse remodeling in infarcted murine myocardium

Transplantation of skeletal myoblasts secreting an IL-1 inhibitor modulates adverse remodeling in infarcted murine myocardium

The Role of Tumor Necrosis Factor-alpha (TNF-α) in Skeletal Muscle Regeneration

IL-1β Impairs Insulin-Like Growth Factor I-Induced Differentiation and Downstream Activation Signals of the Insulin-Like Growth Factor I Receptor in Myoblasts

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