Toll-like receptor 4 participates in gastric mucosal protection through Cox-2 and PGE2

Dig Liver Dis. 2010 Jul;42(7):472-6. doi: 10.1016/j.dld.2009.10.007. Epub 2009 Dec 16.

Abstract

Aim: 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.

Conclusion: 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).

MeSH terms

  • Animals
  • Chemokine CXCL2 / metabolism
  • Cyclooxygenase 2 / metabolism
  • Ethanol
  • Female
  • Gastric Mucosa / metabolism*
  • Macrophages / metabolism*
  • Mice
  • Mice, Inbred C3H
  • Mice, Inbred C57BL
  • Signal Transduction
  • Stomach Diseases / chemically induced
  • Stomach Diseases / pathology*
  • Toll-Like Receptor 4 / metabolism*

Substances

  • Chemokine CXCL2
  • Cxcl2 protein, mouse
  • Tlr4 protein, mouse
  • Toll-Like Receptor 4
  • Ethanol
  • Ptgs2 protein, mouse
  • Cyclooxygenase 2