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

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 E₂ (PGE₂) 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 PGE₂ 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 PGE₂.

Abbreviations: TLR4, Toll-like receptor 4, Cox-1, cyclooxygenase-1, Cox-2, cyclooxygenase-2, PGE₂, prostaglandin E₂, ELISA, enzyme-linked immunosorbent assay, LPS, lipopolysaccharide, IF, immunofluorescent, PAMPs, pathogen-associated molecular patterns, DAMPs, damage-associated molecular patterns, HMGB1, high mobility group box 1, MIP-2, macrophage-inflammatory protein-2

Keywords: Cox-2, Gastric cytoprotection, PGE₂, TLRs