BACKGROUND: Toll-like receptors (TLRs) are a group of evolutionarily conserved pattern recognition receptors involved in the activation of the immune system in response to various pathogens. In this study, we elucidated the relationship between activation of TLR4 and liver injury in partial hepatic ischemia/reperfusion (I/R) injury in mice. METHODS: BALB/c mice were used in a model of partial hepatic I/R injury, and the changes of TLR4 gene expression in ischemic liver lobes were detected with real-time polymerase chain reaction (RT-PCR). The levels of plasma ALT and endotoxin in the portal vein were measured. TLR4-deficient mice (C3H/Hej) and wild type mice (C3H/Heouj) were used in a model of I/R injury; liver function impairment and the level of serum TNF-alpha were observed. RESULTS: After one hour ischemia, the expression of TLR4 mRNA increased at the 1st, 3rd hour of reperfusion, indicating the value of deltaCt (1st hour: 1.21+/-0.87 vs. 5.85 +/-1.07, t=13.72, P<0.01; 3rd hour: 0.85+/-0.92 vs. 6.11+/-1.24, t=16.33, P<0.01). No endotoxemia developed in every group of mice. At the 3rd hour of reperfusion, the level of serum TNF-alpha was significantly higher than that of sham group (Hej: 152+/-43 pg/ml vs. 18+/-10 pg/ml, t=5.26, P<0.01; Heouj: 249+/-52 pg/ml vs. 25+/-13 pg/ml, t=7.24, P<0.01). At the 1st, 3rd hour reperfusion, the level of plasmid ALT in Hej mice was lower than that in Heouj mice (1st hour 662+/-106 U/L vs. 1216+/-174 U/L, t=4.21, P<0.01; 3rd hour 1145+/-132 U/L vs. 2958+/-187 U/L, t=13.72, P<0.01). The level of serum TNF-alpha was lower than that in Heouj mice (152+/-43 U/L vs. 249+/-52 U/L, t=3.94, P<0.01) at the 3rd hour reperfusion. CONCLUSION: TLR4 activation causes partial hepatic I/R injury through release of TNF-alpha.
BACKGROUND: Toll-like receptors (TLRs) are a group of evolutionarily conserved pattern recognition receptors involved in the activation of the immune system in response to various pathogens. In this study, we elucidated the relationship between activation of TLR4 and liver injury in partial hepatic ischemia/reperfusion (I/R) injury in mice. METHODS: BALB/c mice were used in a model of partial hepatic I/R injury, and the changes of TLR4 gene expression in ischemic liver lobes were detected with real-time polymerase chain reaction (RT-PCR). The levels of plasma ALT and endotoxin in the portal vein were measured. TLR4-deficientmice (C3H/Hej) and wild type mice (C3H/Heouj) were used in a model of I/R injury; liver function impairment and the level of serum TNF-alpha were observed. RESULTS: After one hour ischemia, the expression of TLR4 mRNA increased at the 1st, 3rd hour of reperfusion, indicating the value of deltaCt (1st hour: 1.21+/-0.87 vs. 5.85 +/-1.07, t=13.72, P<0.01; 3rd hour: 0.85+/-0.92 vs. 6.11+/-1.24, t=16.33, P<0.01). No endotoxemia developed in every group of mice. At the 3rd hour of reperfusion, the level of serum TNF-alpha was significantly higher than that of sham group (Hej: 152+/-43 pg/ml vs. 18+/-10 pg/ml, t=5.26, P<0.01; Heouj: 249+/-52 pg/ml vs. 25+/-13 pg/ml, t=7.24, P<0.01). At the 1st, 3rd hour reperfusion, the level of plasmid ALT in Hej mice was lower than that in Heouj mice (1st hour 662+/-106 U/L vs. 1216+/-174 U/L, t=4.21, P<0.01; 3rd hour 1145+/-132 U/L vs. 2958+/-187 U/L, t=13.72, P<0.01). The level of serum TNF-alpha was lower than that in Heouj mice (152+/-43 U/L vs. 249+/-52 U/L, t=3.94, P<0.01) at the 3rd hour reperfusion. CONCLUSION:TLR4 activation causes partial hepatic I/R injury through release of TNF-alpha.
Authors: X-D Shen; B Ke; H Ji; F Gao; M C S Freitas; W W Chang; C Lee; Y Zhai; R W Busuttil; J W Kupiec-Weglinski Journal: Am J Transplant Date: 2012-03-19 Impact factor: 8.086