Toll-like receptor 4 participates in gastric mucosal protection through Cox-2 and PGE2.
OBJECTIVE
To elucidate the role of Toll-like receptors (TLRs) in gastric cytoprotection after ethanol injury.


METHODS
C57BL/6J, C3H/HeOuJ and C3H/HeJ mice were used. All mice were killed 4h after ethanol administration. TLR4, cyclooxygenase-2 (Cox-2) and prostaglandin E(2) (PGE(2)) expression were measured by immunohistochemistry, western blotting and enzyme-linked immunosorbent assay (ELISA) separately.


RESULTS
The expression of TLR4 increased in C57BL/6J mice stomach 4h after ethanol injury. The cells expressing TLR4 included Cox-2 expressing cells and macrophages. The injury in C3H/HeJ mice was more severe than in C3H/HeOuJ mice 4h after ethanol injury. The expression of Cox-2 and PGE(2) only increased in C3H/HeOuJ mice. The number of macrophages and the expression of macrophage-inflammatory protein-2 (MIP-2) also increased only in C3H/HeOuJ mice.


CONCLUSIONS
TLR4 signal is activated in mice stomach 4h after ethanol injury. The protective effects of TLR4 signalling are mediated through the induction of Cox-2 expression and the production of PGE(2).
Zhang
Yan
Y
Division of Gastroenterology, West China Hospital of Sichuan University, GuoXue Street 37, Chengdu 610041, Sichuan, China. fengyixx@sohu.com
Chen
Huan
H
Yang
Li
L
D000818:Animals; D054426:Chemokine CXCL2 / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D000431:Ethanol; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D015398:Signal Transduction; D013272:Stomach Diseases / Q000139:chemically induced / Q000473:pathology*; D051197:Toll-Like Receptor 4 / Q000378:metabolism*
D054426:Chemokine CXCL2; C404915:Cxcl2 protein, mouse; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D000431:Ethanol; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2