The mRNA expression patterns of tumor necrosis factor-alpha and TNFR-I in some vital organs after thermal injury

Abstract

Aim: 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.

Conclusion: 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.

Figure 1

Semiquantitive analysis of tumor necrosis factor-α (TNF-α) mRNA in various organs after thermal injury. Values are reported as the ratio of TNF-α to β-actin signals. ^aP < 0.05 and ^bP < 0.01 as compared to the control values.

Figure 2

TNF-α protein levels in various organs after thermal injury. Values are reported as pg/mg protein. ^aP < 0.05 as com-pared to the control values.

Figure 3

Semiquantitive analysis of tumor necrosis factor-α receptor-I (TNFR-I) mRNA in observed organs after thermal injury. Values are reported as the ratio of TNFR-I to β-actin signals. ^aP < 0.05 as compared to the control values.

Figure 4

mRNA expression ratio of tumor necrosis factor-α to TNFR-I (T/R ratio) in observed organs after thermal injury. ^aP < 0.05 and ^bP < 0.01 as compared to the control values.