The significance of changes in high mobility group-1 protein mRNA expression in rats after thermal injury.
There has been a widespread impression that tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) mediate the toxicity of high doses of lipopolysaccharide (LPS, endotoxin) and are key factors in septic shock. However, the clinical efficacy of treatment with antagonists of TNF-alpha and IL-1beta is still controversial, suggesting that mediators other than TNF-alpha and IL-1beta might contribute causally to endotoxin-induced death. Recent studies implicated high mobility group-1 (HMG-1) protein as a late mediator of endotoxin lethality in mice. However, the role of HMG-1 in mediating multiple organ damage-associating trauma has not been studied. This study was designed to investigate changes in HMG-1 gene expression in vital organs, and its potential role in mediating multiple organ damage following major burns. Wistar rats were subjected to a 35 percent full-thickness thermal injury, and randomly divided into three groups as follows: normal controls (n = 7), thermal injury (n = 24), and recombinant bactericidal/permeability-increasing protein (rBPI21) treatment (n = 12). Tissue samples from liver and lungs were collected to measure tissue endotoxin levels and HMG-1 mRNA expression. In addition, blood samples were obtained for measurement of organ function parameters. Our data demonstrated a significant increase in HMG-1 gene expression in tissues at 24 h postburn, which remained markedly elevated up to 72 h after thermal injury (P< 0.05-0.01). Treatment with rBPI21 could significantly decrease tissue HMG-1 mRNA expression in the liver and lung (P < 0.01). In addition, there were high positive correlations between hepatic HMG-1 mRNA and serum aminoleucine transferase (ALT) and aspartate aminotransferase (AST) levels, and also between pulmonary HMG-1 mRNA and myeloperoxidase activities (P < 0.05-0.01). Taken together, these findings indicate that thermal injury per se can markedly enhance HMG-1 gene expression in various organs. Up-regulation of HMG-1 expression may be involved in the pathogenesis of endogenous endotoxin-mediated multiple organ damage secondary to major burns.
Fang
Wen-Hui
WH
The Department of Microbiology and Immunology, Trauma Research Center, Postgraduate Medical College, Beijing, People's Republic of China.
Yao
Yong-Ming
YM
Shi
Zhi-Guo
ZG
Yu
Yan
Y
Wu
Ye
Y
Lu
Lian-Rong
LR
Sheng
Zhi-Yong
ZY
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D000890:Anti-Infective Agents / Q000494:pharmacology; D023181:Antimicrobial Cationic Peptides; D001219:Aspartate Aminotransferases / Q000097:blood; D001798:Blood Proteins / Q000494:pharmacology; D002056:Burns / Q000150:complications / Q000201:enzymology / Q000235:genetics*; D004731:Endotoxins / Q000633:toxicity; D015870:Gene Expression; D024243:HMGB1 Protein / Q000235:genetics*; D008099:Liver / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins; D009102:Multiple Organ Failure / Q000209:etiology; D009195:Peroxidase / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
D000890:Anti-Infective Agents; D023181:Antimicrobial Cationic Peptides; D001798:Blood Proteins; D004731:Endotoxins; D024243:HMGB1 Protein; D008565:Membrane Proteins; D012333:RNA, Messenger; C021623:bactericidal permeability increasing protein; D009195:Peroxidase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase