Physiological role of tumor necrosis factor alpha in traumatic muscle injury.
degenerative and regenerative roles of tumor necrosis factor alpha (TNF-alpha), a pro-inflammatory cytokine with pleiotropic functions, were investigated by using TNF receptor 1 and 2 double knockout (TNFR-DKO) and TNF-alpha antibody neutralized mice following traumatic freeze injury to the tibialis anterior muscle. In wild-type control mice, TNF-alpha mRNA transcripts and protein increased following injury and gradually returned to control (uninjured) levels by 13 days. A reduction in MyoD mRNA expression occurred in TNF-alpha-deficient mice, although there were no visible differences in MyoD immunostaining or histological characteristics in regenerating muscles. At 5 days post-injury, the reductions in isometric strength in TNFR-DKO and TNF-alpha-depleted mice did not differ from that of wild-type mice but by 13 days after injury, the TNFR-DKO and TNF-alpha-depleted mice exhibited strength deficits twice that of wild-type mice (i.e., 27-31% vs 13%). Muscle injury was also accompanied by increased expression of interleukin-6 (IL-6), but IL-6-deficient mice demonstrated MyoD expression and recovery of isometric strength similar to that of wild-type mice. These data indicate that TNF-alpha is involved in the recovery of muscle function after traumatic muscle injury, and this effect might be associated with modulation of muscle regulatory genes, including MyoD.
Warren
Gordon L
GL
Department of Physical Therapy, Georgia State University, Atlanta, Georgia, USA.
Hulderman
Tracy
T
Jensen
Nancy
N
McKinstry
Michael
M
Mishra
Michael
M
Luster
Michael I
MI
Simeonova
Petia P
PP
D000818:Animals; D000906:Antibodies / Q000276:immunology / Q000494:pharmacology; D015870:Gene Expression; D005838:Genotype; D007150:Immunohistochemistry; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D007537:Isometric Contraction / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D018482:Muscle, Skeletal / Q000187:drug effects / Q000293:injuries / Q000378:metabolism*; D017570:MyoD Protein / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology / Q000502:physiology*
D000906:Antibodies; D015850:Interleukin-6; D017570:MyoD Protein; D012333:RNA, Messenger; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha