The mRNA expression patterns of tumor necrosis factor-alpha and TNFR-I in some vital organs after thermal injury.
OBJECTIVE
To investigate changes of tumor necrosis factor-alpha (TNF-alpha) and TNFR-I expression in vital organs and their significance in the pathogenesis of multiple organ damage associated with endogenous endotoxin following major burns.


METHODS
Wistar rats subjected to a 35 % full-thickness scald injury were sacrificed at 12 h, 24 h, 48 h, and 72 h postburn, respectively. Meanwhile, eight rats were taken as normal controls. Tissue samples from liver, spleen, kidney, lung and intestine were collected to assay tissue endotoxin levels and measure TNF-alpha and TNFR-I expression. In addition, blood samples were obtained for the determination of organ function parameters.


RESULTS
Endotoxin levels in liver, spleen and lung increased markedly after thermal injury, with the highest level in liver. The gene expression of TNF-alpha in liver, lung and kidney was up-regulated after thermal injury, while the TNFR-I mRNA expression in liver, lung, kidney and intestine was shown decreased throughout the observation period. Thus, the mRNA expression ratio of TNF-alpha to TNFR-I was significantly increased postburn, particularly in pulmonary tissue (67-fold). In addition, the significant correlations between the expression of TNFR-I or the expression ratio of TNF-alpha/TNFR mRNA in liver tissue and serum aspartate aminotransferase levels were noted (P<0.05-0.01). Similar results were also obtained between pulmonary TNF-alpha mRNA expression and myeloperoxidase activities (P<0.01), whereas there was a highly negative correlation between levels of renal TNFR-I mRNA expression and serum creatinine.


CONCLUSIONS
Burn injury could result in the translocation of gut-derived endotoxin that was mainly distributed in the liver, spleen and lung. The translocated endotoxin then made the expression of TNF-alpha and TNFR-I mRNA up-regulated and down-regulated respectively in various organs, which might be involved in the pathogenesis of multiple organ damage following burns.
Fang
Wen-Hui
WH
Department of Microbiology and Immunology, Burns Institute, 304th Hospital of PLA, Beijing 100037, China.
Yao
Yong-Ming
YM
Shi
Zhi-Guo
ZG
Yu
Yan
Y
Wu
Ye
Y
Lu
Lian-Rong
LR
Sheng
Zhi-Yong
ZY
D000818:Animals; D015703:Antigens, CD / Q000235:genetics*; D001483:Base Sequence; D002056:Burns / Q000150:complications / Q000235:genetics* / Q000382:microbiology / Q000503:physiopathology; D004247:DNA / Q000235:genetics; D004731:Endotoxins / Q000378:metabolism; D015870:Gene Expression; D006090:Gram-Negative Bacteria / Q000302:isolation & purification / Q000472:pathogenicity; D016905:Gram-Negative Bacterial Infections / Q000209:etiology / Q000503:physiopathology; D007422:Intestines / Q000503:physiopathology; D007668:Kidney / Q000503:physiopathology; D008099:Liver / Q000503:physiopathology; D008168:Lung / Q000503:physiopathology; D008297:Male; D009102:Multiple Organ Failure / Q000209:etiology / Q000235:genetics / Q000382:microbiology / Q000503:physiopathology; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics*; D047888:Receptors, Tumor Necrosis Factor, Type I; D018805:Sepsis / Q000209:etiology / Q000503:physiopathology; D014018:Tissue Distribution; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
D015703:Antigens, CD; D004731:Endotoxins; D012333:RNA, Messenger; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D014409:Tumor Necrosis Factor-alpha; D004247:DNA