TNF-alpha mRNA expression in diaphragm muscle after endotoxin administration.
We studied gene expression and production of TNF-alpha in the diaphragm tissue and changes of muscle contractile properties after endotoxin injection (Escherichia coli, 20 mg/kg) in 88 rats. We assessed the muscle contractile properties by force-frequency curves and twitch kinetics using dissected diaphragm muscle strips. The peak tensions of force-frequency curves decreased from control values (2.15 +/- 0.2 kg/cm2) up to 4 h (0.81 +/- 0.17, p < 0.001), and then increased at 6 h (1.36 +/- 0.19, p < 0.05) after endotoxin injection. The cytotoxic activity on L929 cells in arterial blood samples maximally increased at 2 h (p < 0.001), then decreased to 6 h (p < 0.05). TNF-alpha mRNA in diaphragm tissue was detected by Northern blot method at 1 and 1.5 h, and the immunolocalization of TNF-alpha was evaluated at 2 and 4 h by immunohistochemistry in the muscle tissues. Furthermore, preinjection with anti-m TNF-alpha antibody prevented the decrement of force-frequency curves after endotoxin injection of 10 microliters/kg. From this evidence that TNF-alpha gene expression and production occurred in the diaphragm tissue, but anti-m TNF-alpha antibody preinjection prevented the deterioration of diaphragm muscle contractile properties, we suggest that TNF-alpha may act on muscle cells extracellularly.
Shindoh
C
C
First Department of Internal Medicine, Tohoku University School of Medicine, Sendai, Japan.
Hida
W
W
Ohkawara
Y
Y
Yamauchi
K
K
Ohno
I
I
Takishima
T
T
Shirato
K
K
D000704:Analysis of Variance; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D003964:Diaphragm / Q000737:chemistry / Q000187:drug effects* / Q000502:physiology; D004731:Endotoxins / Q000633:toxicity*; D004926:Escherichia coli; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000502:physiology; D007150:Immunohistochemistry; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D012333:RNA, Messenger / Q000032:analysis / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism
D000906:Antibodies; D004731:Endotoxins; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha