The relationship between activation of TLR4 and partial hepatic ischemia/reperfusion injury in mice.
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.


CONCLUSIONS
TLR4 activation causes partial hepatic I/R injury through release of TNF-alpha.
Wang
Lin
L
Department of Pediatrics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China. whs1898@public.wh.hb.cn
Xu
Jian-Bo
JB
Wu
He-Shui
HS
Zhang
Jin-Xiang
JX
Zhang
Jin-Hui
JH
Tian
Yuan
Y
Wang
Chun-You
CY
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D004195:Disease Models, Animal; D004731:Endotoxins / Q000097:blood; D005500:Follow-Up Studies; D005786:Gene Expression Regulation; D008099:Liver / Q000098:blood supply* / Q000378:metabolism; D008107:Liver Diseases / Q000235:genetics* / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D011169:Portal Vein; D012333:RNA, Messenger / Q000235:genetics*; D015427:Reperfusion Injury / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051197:Toll-Like Receptor 4 / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D004731:Endotoxins; D012333:RNA, Messenger; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; D000410:Alanine Transaminase