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.
Department of Physical Therapy, Georgia State University, Atlanta, Georgia, USA.
Gordon L
GL
Warren
Tracy
T
Hulderman
Nancy
N
Jensen
Michael
M
McKinstry
Michael
M
Mishra
Michael I
MI
Luster
Petia P
PP
Simeonova
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