Department of Medicine, Baylor College of Medicine, Houston, Texas 77030
Submitted 30 September 2002 ; accepted in final form 16 April 2003
![]() |
ABSTRACT |
---|
![]() ![]() ![]() ![]() ![]() ![]() |
---|
cytokine; cell cycle; satellite cells; serum response factor; c-fos
In addition to macrophages, myocytes are also a source of TNF-.
Myocytes constitutively synthesize TNF-
(38). During muscle injury,
TNF-
is not only released in large quantity by infiltrating macrophages
but also synthesized at increased levels by injured muscle fibers. Strong
expression of TNF-
by injured muscle fibers is detected in human
muscles biopsied from patients of inflammatory myopathies or Duchenne muscular
dystrophy (10,
48) and in the injured muscles
of experimental animals during the course of regeneration
(8,
54,
56). The level of TNF-
expression in injured muscle fibers is not correlated to the grade of
inflammation (48), suggesting
that upregulation of TNF-
expression in injured muscle fibers is not a
simple response to inflammation. Similar responses may be evoked in the
absence of overt pathology. In healthy humans, acute increases in circulating
TNF-
levels occur after strenuous exercise
(35) and possibly originate
from skeletal muscle (45).
Clearly, muscle regeneration proceeds in a high-TNF-
environment, which
makes TNF-
a relevant factor in muscle regeneration.
TNF- has pleiotropic functions
(50). In addition to mediating
inflammatory, cytotoxic/apoptotic, and muscle protein catabolic responses,
TNF-
modulates growth and differentiation in various cell types.
TNF-
and its receptors are detected in embryos and neonatal animals
(16,
24,
34,
55). Repeated injections of
neutralizing antibodies to TNF-
into pregnant mice resulted in growth
retardation of the fetus (11).
The seemingly normal development of TNF-
or TNF-
receptor
knockout mice does not refute this observation, because the compensatory
increase of other cytokines such as IL-1, IL-12 and IFN-
can largely
replace the role of TNF-
(12,
21,
46). Nevertheless, closer
examinations of TNF-
signaling-impaired mice revealed that TNF-
is important for muscle development and regeneration. Mice deficient in
TNF-
receptor-associated factor 2, an important signaling molecule for
TNF-
receptor activation
(22,
43), are born with a
systematically smaller muscle mass
(30). TNF-
gene
knockout in dystrophin-deficient mice (TNF-/mdx) resulted in a
significantly lower muscle mass than TNF+/mdx mice
(44) after a period of active
muscle regeneration (26,
31). TNF-
receptor
double knockout impairs muscle strength recovery after freeze-induced injury
in adult mice (54). These
observations suggest a physiological role for TNF-
in muscle
development and regeneration.
During muscle regeneration, normally quiescent satellite cells are
activated to enter the cell cycle and proliferate. A subset of the daughter
satellite cells then differentiates and becomes part of the repaired or
enhanced muscle fibers. Certain growth factors or cytokines can modulate
satellite cell proliferation by activating satellite cells to enter the cell
cycle (competence factor) or enhancing satellite cell proliferation once it
has been initiated (progression factor)
(7,
47). Previous studies
evaluated TNF- effects on myocyte proliferation in vitro using myogenic
cell lines. However, the results were inconsistent with both a stimulatory
effect reported in the C2C12 myoblast cell line
(25) and an inhibitory effect
reported in the L8 myoblast cell line
(23). More importantly, there
are no data on whether TNF-
affects satellite cell activation. The
present study was designed to determine whether TNF-
affects DNA
synthesis and cell cycle progression in primary myoblasts and whether
TNF-
stimulates satellite cell activation in adult mice. Here we show
evidence that TNF-
is a mitogen in skeletal muscle and that TNF-
stimulates expression of the early response gene c-fos via activating
serum response factor (SRF).
![]() |
METHODS |
---|
![]() ![]() ![]() ![]() ![]() ![]() |
---|
DNA determination. Total DNA was isolated from primary myoblasts by using the DNAzol reagent (Invitrogen, Carlsbad, CA) according to the manufacturer's protocol. DNA concentration was determined by measuring the fluorescence emission of DNA in a Hoechst dye solution containing 0.1 µg/ml Hoechst 33258, 0.2 M NaCl, 10 mM Tris-Cl, and 1 mM EDTA (pH 7.4) using the DyNA Quant 200 fluorometer (Pharmacia).
Flow cytometry analysis of cell cycle in myoblasts. Murine
recombinant TNF- (Roche, Indianapolis, IN) or vehicle was incubated
with proliferating rat primary myoblasts (
50% confluent) for 16 h,
followed by a 30-min pulse labeling with 10 µM BrdU. Myoblasts were
harvested by brief trypsinization and fixed in cold 70% ethanol overnight.
Cells were pelleted, resuspended, and incubated in 0.1 M HCl containing 0.5%
Triton X-100 on ice for 10 min. Cells were pelleted, resuspended in distilled
water, and boiled for 5 min and quickly chilled on ice. After being washed in
PBS containing 0.5% Triton X-100, cells were incubated with 5 µg/ml
anti-BrdU-FITC (Roche) in PBS containing 0.1% BSA in the dark at room
temperature for 30 min. Cells were then stained with 5 µg/ml propidium
iodide containing 200 µg/ml RNase and analyzed with an EPICS XL-MCL flow
cytometer (Coulter Electronics, Hialeah, FL).
Animal use. Experimental protocols were approved in advance by the
Animal Protocol Review Committee of the Baylor College of Medicine. Six- to
eight-week-old adult male mice (ICR) were injected intraperitoneally with 50
µg/kg murine recombinant TNF- (BD Biosciences) and 16 h later with
50 mg/kg BrdU for a 2-h pulse labeling. Mice were deeply anesthetized by
intraperitoneal injection of 85 mg/kg pentobarbital sodium. Soleus and
diaphragm muscles were excised for immunofluorescence staining, and the
anesthetized animals were killed by rapid exsanguinations.
Immunofluorescence staining. Frozen muscle sections (5 µm) were prepared and submerged in 3.7% formaldehyde for 15 min. After three 10-min washes in PBS, an incubation in 2 M HCl was carried out for 20 min at 37°C and again washed three times. Muscle sections were blocked in a blocking buffer (5% chicken serum in PBS) for 1 h at room temperature. Incubation with primary antibodies, anti-BrdU-FITC (Roche) and anti-laminin (Sigma, St. Louis, MO), was done for 1 h at 37°C with 1:20 and 1:25 dilution, respectively. After three washes, incubation with a rhodamine-conjugated anti-rabbit second antibody was carried out for 1 h at 37°C. The sections were washed again three times and incubated with 0.1% 4',6'-diamidino-2-phenylindole (DAPI) at room temperature for 13 min. After a final three washes, the sections were mounted. A Zeiss Axiophot fluorescence microscope coupled to a digital camera utilizing Adobe Photoshop software was used to acquire the images.
Electrophoretic mobility shift assay. Electrophoretic mobility
shift assay (EMSA) was carried out in a binding assay buffer containing 5 mM
Tris·HCl (pH 7.5), 100 mM NaCl, 0.3 mM dithiothreitol, 5 mM
MgCl2, 10% glycerol, 2 µg of BSA, 0.2% NP-40, and 1 µg of
poly(dG-dC)-poly (dG-dC). A DNA probe replicating the serum response element
(SRE) present in the c-fos gene and the flanking sequence
(5'-ACAGGATGTCCATATTAGGACATCTGCG-3') was labeled with
[-32P]dATP (3,000 Ci/mmol; Amersham Pharmacia, Arlington
Heights, IL) using the Klenow fragment. After 20-min preincubation of 5 µg
of nuclear extract prepared according to Andrews and Faller
(1) in the assay buffer, 1 ng
(10,00015,000 cpm) of labeled probe was added and incubation was
continued for 30 min on ice. For supershift assay, a specific anti-SRF (Santa
Cruz Biotechnology) or a control antibody was added for an additional 20-min
incubation. The reaction mixtures were resolved on 4.5% polyacrylamide gels.
Protein concentration of the nuclear extracts was determined by the Bio-Rad
protein assay kit.
Reporter gene assay. C2C12 myoblasts were
transfected with either a plasmid construct containing the minimal promoter of
the c-fos gene without the SRE (c-fos56) or a
construct containing the c-fos promoter including the SRE
(c-fos-SRE) by using the Lipofectamine reagent (Invitrogen). These
constructs were gifts from Dr. Robert J. Schwartz (Baylor College of
Medicine). At 20 h posttransfection, myoblasts were incubated with TNF-
and then lysed at 3, 6, and 9 h for luciferase assay. Light intensity was
measured for 10 s in a Turner Designs TD-20/20 Luminometer and expressed in
arbitrary relative light units (RLU). Experiments were carried out in
duplicate. RLU were normalized to total protein content determined by the
Bio-Rad protein assay kit.
![]() |
RESULTS |
---|
![]() ![]() ![]() ![]() ![]() ![]() |
---|
|
To verify this finding, we incubated proliferating primary myoblasts with 6
ng/ml TNF- for 16 h and subjected them to a 30-min pulse labeling with
10 µM BrdU. Myoblasts were then stained with anti-BrdUFITC and propidium
iodide. The stained myoblasts were analyzed by flow cytometry. TNF-
increased the number of myoblasts incorporating BrdU, which is represented by
cells in quadrant 2 of Fig.
2A, from
21% of total cells in control to 35%
(n = 3, Fig.
2B). These results suggest that TNF-
stimulates
DNA synthesis by accelerating cell cycle progression from the G1
phase to S phase. This increase is comparable to the increase of total DNA
content illustrated in Fig.
1.
|
To determine whether TNF- is capable of activating quiescent
satellite cells to enter the cell cycle, we evaluated DNA synthesis in
satellite cells by monitoring BrdU incorporation in vivo. Murine recombinant
TNF-
(50 µg/kg) was administered via intraperitoneal injection to
6-wk-old adult mice and the mice were pulse labeled 16 h later with
intraperitoneally injected 50 mg/kg BrdU for 2 h. By modifying the methods
published by Mozdziak et al.
(32) and Cornelison and Wold
(9), immunofluorescence
staining with a specific anti-BrdU antibody was performed to detect
proliferating satellite cells in frozen muscle sections. To determine whether
an anti-BrdU-stained cell is satellite cell, we took advantage of the
characteristic localization of satellite cells, which is underneath or
embedded in the basal lamina of myofibers
(3), by costaining muscle
sections with anti-laminin to outline the basal lamina. In addition,
costaining with DAPI verifies that the anti-BrdU staining belongs to nuclei of
single cells, which rules out the possibility that these cells are vascular
endothelial cells. Figure 3
shows an example of a BrdU-incorporated satellite cell. We observed no
satellite cell that incorporated BrdU in nine soleus muscle sections from
three control mice, consistent with the notion that adult satellite cells are
quiescent. However, an average of 6 ± 1.3 BrdU-stained satellite cells
per section were observed in nine soleus sections from three
TNF-
-injected mice. Similar results were observed in diaphragm sections
(data not shown). The morphological integrity was monitored by hematoxylin and
eosin staining of the muscle sections, and no abnormality suggesting muscle
injury was seen.
|
SRF is known to stimulate c-fos gene expression by binding to the
SRE motif present in the c-fos gene promoter, and c-fos is
an important early response gene involved in cell growth regulation
(36). We therefore evaluated
TNF- effect on the binding activity of SRF to the SRE in the
c-fos gene promoter by using EMSA. We took advantage of
C2C12 myoblasts that respond to TNF-
with
increased proliferation (25)
and tolerate standard transfection procedures better than primary myoblasts.
TNF-
rapidly stimulated binding activity in nuclear extracts of
C2C12 myoblasts. SRF binding to a DNA fragment that
replicates the c-fos SRE was increased within 15 min of TNF-
exposure and returned to control level at 60 min
(Fig. 4). To determine whether
enhanced SRF binding results in a stimulation of c-fos gene
expression, TNF-
effect on c-fos SRE-controlled luciferase
reporter gene expression in C2C12 myoblasts was studied
by transient transfection. We observed a stimulation of c-fos
SRE-controlled luciferase activity by TNF-
, most notably at 6 h of
TNF-
exposure (Fig. 5),
whereas the minimal c-fos promoter without SRE did not respond to
TNF-
. These results suggest that TNF-
stimulation of satellite
cell proliferation may involve activation of c-fos gene
expression.
|
|
![]() |
DISCUSSION |
---|
![]() ![]() ![]() ![]() ![]() ![]() |
---|
We have demonstrated that TNF- stimulates DNA synthesis at a
concentration range from 2 to 6 ng/ml, which was shown previously to evoke
signaling events mediated by TNF-
receptor activation in cultured
myocytes without inducing necrotic or apoptotic death
(27,
29). The fall of the
stimulatory effect of 20 ng/ml TNF-
on DNA content is consistent with
the reported cytotoxicity of TNF-
on myocytes at high concentrations
(39). These observations
reiterate the concentration dependence of TNF-
actions.
The TNF- dose (50 µg/kg ip) we used to evoke satellite cell
activation is lower than those used to induce muscle protein loss or
apoptosis, which require repeated doses of 100500 µg/kg via the same
route (6,
13,
14). Histological study did
not see signs of muscle damage, so we can rule out the possibility that
satellite cell activation is a response to muscle injury. Although TNF-
level in injured muscle is unknown, the acute surge of TNF-
expression
after injury could create a local TNF-
concentration high enough to
activate satellite cells. After acute muscle injury, TNF-
expression
increases within 5 h and reaches the peak level around 24 h before returning
to the basal level gradually
(54); the onset of peak
TNF-
level parallels the time when satellite cells are activated
(15), supporting a causal
relationship between the two events.
We observed 6 ± 1.3 activated satellite cells in soleus sections
from TNF- injected mice. To put this number in perspective, we
estimated the number of total satellite cells possibly present in a section.
The adult soleus contains about 5,000 satellite cells/mm3
(40). The cross-sectional area
of our soleus samples averaged 0.65 mm2. Each 5-µm transverse
section gives an average volume of 0.0033 mm3. Thus each section
averaged 16.5 satellite cells (5,000 x 0.0033), suggesting that a
substantial number of satellite cells were activated by TNF-
.
TNF- stimulation of myoblast proliferation appears to involve
multiple signaling pathways. Guttridge et al.
(19) demonstrated previously
that NF-
B stimulates cell cycle progression from the G1 to S
phase by regulating the expression of the cyclin D1 gene. TNF-
activates NF-
B in skeletal muscle myoblasts
(28,
41), and TNF-
stimulation of cell cycle progression is likely to involve mediation by
NF-
B. We have further demonstrated that the mitogenic effect of
TNF-
may also involve signaling through SRF. SRF, a transcription
factor, activates gene transcription by binding as a homodimer to a DNA motif
known as the SRE (or CArG box)
(33). SRE mediates increased
expression of immediate-early genes, including c-fos, in cells
treated with growth factors or cytokines
(51). Our observations that
TNF-
stimulates SRF binding to the SRE of the c-fos gene
promoter and c-fos SRE-directed luciferase reporter gene expression
suggest that the mitogenic effect of TNF-
is likely to involve
activation of specific immediate-early genes. Our experiments were carried out
in a growth medium supplied with 20% newborn bovine serum. SRF responds to
serum growth factors (51). The
basal activity of SRF seen in our transfection experiments may reflect the
presence of serum growth factors. Growth factors regulate SRF activity via
cofactors that interact with SRF
(52) without changing its
DNA-binding activity (17,
42,
51). The ability of
TNF-
to enhance SRF binding to SRE is unique compared with growth
factors.
The mitogenic effect of TNF- described in the present study may be
an integrated part of a comprehensive tissue remodeling effect of TNF-
in skeletal muscle, in addition to the previously reported TNF-
stimulation of muscle catabolism
(37) and differentiation
(28). The catabolic effect is
likely to promote the degradation of necrotic tissue, whereas the
proliferation- and differentiation-stimulatory effects promote regeneration.
Such a scenario suggests that TNF-
has a physiological role in the
maintenance of skeletal muscle and that caution needs to be exercised in using
anti-TNF-
strategies to control inflammatory and other conditions.
![]() |
DISCLOSURES |
---|
![]() |
ACKNOWLEDGMENTS |
---|
![]() |
FOOTNOTES |
---|
The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
![]() |
REFERENCES |
---|
![]() ![]() ![]() ![]() ![]() ![]() |
---|
2. Blau HM, Pavlath GK, Hardeman EC, Chiu CP, Silberstein L, Webster SG, Miller SC, and Webster C. Plasticity of the differentiated state. Science 230: 758766, 1985.[ISI][Medline]
3. Campion DR. The muscle satellite cell: a review. Int Rev Cytol 87: 225251, 1984.[ISI][Medline]
4. Cantini M and Carraro U. Macrophage-released factor stimulates selectively myogenic cells in primary muscle culture. J Neuropathol Exp Neurol 54: 121128, 1995.[ISI][Medline]
5. Cantini M, Massimino ML, Bruson A, Catani C, Dalla LL, and Carraro U. Macrophages regulate proliferation and differentiation of satellite cells. Biochem Biophys Res Commun 202: 16881696, 1994.[ISI][Medline]
6. Carbo N, Busquets S, van Royen M, Alvarez B, Lopez-Soriano FJ, and Argiles JM. TNF-alpha is involved in activating DNA fragmentation in skeletal muscle. Br J Cancer 86: 10121016, 2002.[ISI][Medline]
7. Chambers RL and McDermott JC. Molecular basis of skeletal muscle regeneration. Can J Appl Physiol 21: 155184, 1996.[Medline]
8. Collins RA and
Grounds MD. The role of tumor necrosis factor-alpha (TNF-alpha) in
skeletal muscle regeneration. Studies in TNF-alpha(-/-) and
TNF-alpha(-/-)/LT-alpha(-/-) mice. J Histochem
Cytochem 49:
9891002, 2001.
9. Cornelison DD and Wold BJ. Single-cell analysis of regulatory gene expression in quiescent and activated mouse skeletal muscle satellite cells. Dev Biol 191: 270283, 1997.[ISI][Medline]
10. De Bleecker JL, Meire VI, Declercq W, and Van Aken EH. Immunolocalization of tumor necrosis factor-alpha and its receptors in inflammatory myopathies. Neuromuscul Disord 9: 239246, 1999.[ISI][Medline]
11. De Kossodo S, Grau GE, Daneva T, Pointaire P, Fossati L, Ody C, Zapf J, Piguet PF, Gaillard RC, and Vassalli P. Tumor necrosis factor alpha is involved in mouse growth and lymphoid tissue development. J Exp Med 176: 12591264, 1992.[Abstract]
12. De Maeyer E and De Maeyer-Guignard J. Interferons. In: The Cytokine Handbook, edited by Thomson AW. San Diego, CA: Academic, 1998, p. 491516.
13. Fong Y,
Moldawer LL, Marano M, Wei H, Barber A, Manogue K, Tracey KJ, Kuo G, Fischman
DA, Cerami A, and Lowry SF. Cachectin/TNF or IL-1 alpha induces cachexia
with redistribution of body proteins. Am J Physiol Regul Integr
Comp Physiol 256:
R659R665, 1989.
14. Garcia-Martinez C, Agell N, Llovera M, Lopez-Soriano FJ, and Argiles JM. Tumour necrosis factor-alpha increases the ubiquitinization of rat skeletal muscle proteins. FEBS Lett 323: 211214, 1993.[ISI][Medline]
15. Garry DJ,
Meeson A, Elterman J, Zhao Y, Yang P, Bassel-Duby R, and Williams RS.
Myogenic stem cell function is impaired in mice lacking the forkhead/winged
helix protein MNF. Proc Natl Acad Sci USA
97: 54165421,
2000.
16. Goodwin RG, Anderson D, Jerzy R, Davis T, Brannan CI, Copeland NG, Jenkins NA, and Smith CA. Molecular cloning and expression of the type 1 and type 2 murine receptors for tumor necrosis factor. Mol Cell Biol 11: 30203026, 1991.[ISI][Medline]
17. Greenberg ME, Siegfried Z, and Ziff EB. Mutation of the c-fos gene dyad symmetry element inhibits serum inducibility of transcription in vivo and the nuclear regulatory factor binding in vitro. Mol Cell Biol 7: 12171225, 1987.[ISI][Medline]
18. Grounds MD. Muscle regeneration: molecular aspects and therapeutic implications. Curr Opin Neurol 12: 535543, 1999.[ISI][Medline]
19. Guttridge DC,
Albanese C, Reuther JY, Pestell RG, and Baldwin ASJ. NF-kappaB controls
cell growth and differentiation through transcriptional regulation of cyclin
D1. Mol Cell Biol 19:
57855799, 1999.
20. Hawke TJ and
Garry DJ. Myogenic satellite cells: physiology to molecular biology.
J Appl Physiol 91:
534551, 2001.
21. Hodge-Dufour J,
Marino MW, Horton MR, Jungbluth A, Burdick MD, Strieter RM, Noble PW, Hunter
CA, and Pure E. Inhibition of interferon gamma induced interleukin 12
production: a potential mechanism for the anti-inflammatory activities of
tumor necrosis factor. Proc Natl Acad Sci USA
95: 1380613811,
1998.
22. Hsu H, Shu HB, Pan MG, and Goeddel DV. TRADD-TRAF2 and TRADD-FADD interactions define two distinct TNF receptor 1 signal transduction pathways. Cell 84: 299308, 1996.[ISI][Medline]
23. Ji SQ, Neustrom S, Willis GM, and Spurlock ME. Proinflammatory cytokines regulate myogenic cell proliferation and fusion but have no impact on myotube protein metabolism or stress protein expression. J Interferon Cytokine Res 18: 879888, 1998.[ISI][Medline]
24. Kohchi C, Noguchi K, Tanabe Y, Mizuno D, and Soma G. Constitutive expression of TNF-alpha and -beta genes in mouse embryo: roles of cytokines as regulator and effector on development. Int J Biochem 26: 111119, 1994.[ISI][Medline]
25. Langen RC,
Schols AM, Kelders MC, Wouters EF, and Janssen-Heininger YM. Inflammatory
cytokines inhibit myogenic differentiation through activation of nuclear
factor-kappaB. FASEB J 15:
11691180, 2001.
26. Law DJ and Tidball JG. Dystrophin deficiency is associated with myotendinous junction defects in prenecrotic and fully regenerated skeletal muscle. Am J Pathol 142: 15131523, 1993.[Abstract]
27. Li YP and Reid
MB. NF-B mediates the protein loss induced by TNF-alpha in
differentiated skeletal muscle myotubes. Am J Physiol Regul Integr
Comp Physiol 279:
R1165R1170, 2000.
28. Li YP and
Schwartz RJ. TNF-alpha regulates early differentiation of C2C12 myoblasts
in an autocrine fashion. FASEB J
15: 14131415,
2001.
29. Li YP, Schwartz
RJ, Waddell ID, Holloway BR, and Reid MB. Skeletal muscle myocytes undergo
protein loss and reactive oxygen-mediated NF-kappaB activation in response to
tumor necrosis factor alpha. FASEB J
12: 871880,
1998.
30. MacLachlan TK and Giordano A. TRAF2 expression in differentiated muscle. J Cell Biochem 71: 461466, 1998.[ISI][Medline]
31. McArdle A, Edwards RH, and Jackson MJ. How does dystrophin deficiency lead to muscle degeneration?evidence from the mdx mouse. Neuromuscul Disord 5: 445456, 1995.[ISI][Medline]
32. Mozdziak PE, Schultz E, and Cassens RG. Satellite cell mitotic activity in posthatch turkey skeletal muscle growth. Poult Sci 73: 547555, 1994.[ISI][Medline]
33. Norman C, Runswick M, Pollock R, and Treisman R. Isolation and properties of cDNA clones encoding SRF, a transcription factor that binds to the c-fos serum response element. Cell 55: 9891003, 1988.[ISI][Medline]
34. Ohsawa T and Natori S. Expression of tumor necrosis factor at a specific developmental stage of mouse embryos. Dev Biol 135: 459461, 1989.[ISI][Medline]
35. Ostrowski K,
Rohde T, Asp S, Schjerling P, and Pedersen BK. Pro- and anti-inflammatory
cytokine balance in strenuous exercise in humans. J
Physiol 515:
287291, 1999.
36. Piechaczyk M and Blanchard JM. c-fos proto-oncogene regulation and function. Crit Rev Oncol Hematol 17: 93131, 1994.[ISI][Medline]
37. Reid MB and Li YP. Cytokines and oxidative signaling in skeletal muscle cells. Acta Physiol Scand 171: 225232, 2001.[ISI][Medline]
38. Saghizadeh M,
Ong JM, Garvey WT, Henry RR, and Kern PA. The expression of TNF alpha by
human muscle. Relationship to insulin resistance. J Clin
Invest 97:
11111116, 1996.
39. Sandri M. Apoptotic signaling in skeletal muscle fibers during atrophy. Curr Opin Clin Nutr Metab Care 5: 249253, 2002.[ISI][Medline]
40. Schmalbruch H and Hellhammer U. The number of nuclei in adult rat muscles with special reference to satellite cells. Anat Rec 189: 169175, 1977.[ISI][Medline]
41. Sen CK, Khanna S, Reznick AZ, Roy S, and Packer L. Glutathione regulation of tumor necrosis factor-alpha-induced NF-kappa B activation in skeletal muscle-derived L6 cells. Biochem Biophys Res Commun 237: 645649, 1997.[ISI][Medline]
42. Sheng M, Dougan ST, McFadden G, and Greenberg ME. Calcium and growth factor pathways of c-fos transcriptional activation require distinct upstream regulatory sequences. Mol Cell Biol 8: 27872796, 1988.[ISI][Medline]
43. Shi CS and
Kehrl JH. Activation of stress-activated protein kinase/c-Jun N-terminal
kinase, but not NF-kappaB, by the tumor necrosis factor (TNF) receptor 1
through a TNF receptor-associated factor 2- and germinal center kinase
related-dependent pathway. J Biol Chem
272: 3210232107,
1997.
44. Spencer MJ, Marino MW, and Winckler WM. Altered pathological progression of diaphragm and quadriceps muscle in TNF-deficient, dystrophin-deficient mice. Neuromuscul Disord 10: 612619, 2000.[ISI][Medline]
45. Starkie RL,
Rolland J, Angus DJ, Anderson MJ, and Febbraio MA. Circulating monocytes
are not the source of elevations in plasma IL-6 and TNF-alpha levels after
prolonged running. Am J Physiol Cell Physiol
280: C769C774,
2001.
46. Storkus WJ, Tahara H, and Lotze MT. Interleukin-12. In: The Cytokine Handbook, edited by Thomson AW. San Diego, CA: Academic, 1998, p. 391426.
47. Tatsumi R, Anderson JE, Nevoret CJ, Halevy O, and Allen RE. HGF/SF is present in normal adult skeletal muscle and is capable of activating satellite cells. Dev Biol 194: 114128, 1998.[ISI][Medline]
48. Tews DS and Goebel HH. Cytokine expression profile in idiopathic inflammatory myopathies. J Neuropathol Exp Neurol 55: 342347, 1996.[ISI][Medline]
49. Tidball JG. Inflammatory cell response to acute muscle injury. Med Sci Sports Exerc 27: 10221032, 1995.[ISI][Medline]
50. Tracey KJ and Cerami A. Pleiotropic effects of TNF in infection and neoplasia: beneficial, inflammatory, catabolic, or injurious. In: Tumor Necrosis Factors: Structure, Function, and Mechanism of Action, edited by Aggarwal BB and Vilcek J. New York: Marcel Dekker, 1992, p. 431452.
51. Treisman R. Identification of a protein-binding site that mediates transcriptional response of the c-fos gene to serum factors. Cell 46: 567574, 1986.[ISI][Medline]
52. Treisman R. Ternary complex factors: growth factor regulated transcriptional activators. Curr Opin Genet Dev 4: 96101, 1994.[Medline]
53. Vierck J, O'Reilly B, Hossner K, Antonio J, Byrne K, Bucci L, and Dodson M. Satellite cell regulation following myo-trauma caused by resistance exercise. Cell Biol Int 24: 263272, 2000.[ISI][Medline]
54. Warren GL,
Hulderman T, Jensen N, McKinstry M, Mishra M, Luster MI, and Simeonova PP.
Physiological role of tumor necrosis factor alpha in traumatic muscle injury.
FASEB J 16:
16301632, 2002.
55. Wride MA and Sanders EJ. Expression of tumor necrosis factor-alpha (TNF alpha)-cross-reactive proteins during early chick embryo development. Dev Dyn 198: 225239, 1993.[ISI][Medline]
56. Zador E, Mendler L, Takacs V, de Bleecker J, and Wuytack F. Regenerating soleus and extensor digitorum longus muscles of the rat show elevated levels of TNF-alpha and its receptors, TNFR-60 and TNFR-80. Muscle Nerve 24: 10581067, 2001.[ISI][Medline]