Prostanoids mediate the protective effect of trefoil factor 3 in oxidant-induced intestinal epithelial cell injury: Role of cyclooxygenase-2

Xiaodi Tan*, Yi-Hua Chen, Qian Ping Liu, Frank Gonzalez-Crussi, Xue Li Liu

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

40 Scopus citations


Trefoil factors are small peptides found in several mammalian tissues including gut, respiratory tract and brain. Their physiological function is not well understood. Among them, trefoil factor 3 (intestinal trefoil factor) is known to be cytoprotective in the gut. However, the molecular mechanism and secondary mediators of trefoil factor 3 action are not known. In the present study, we examined whether the cyclooxygenase pathway is involved in trefoil factor 3 action. We showed that trefoil factor 3 significantly induces the production of prostaglandin E 2 and prostaglandin I 2 in IEC-18 cells (an intestinal epithelial cell line) in a dose dependent manner. Western blot and immunohistochemistry revealed that trefoil factor 3 (2.5 μM) up-regulates the expression of cyclooxygenase-2 but not cyclooxygenase-1 in IEC-18 cells. Treating cells with trefoil factor 3 (10 μM) significantly attenuated reactive oxygen species-induced IEC-18 cell injury. This effect is blocked by NS-398 (10 μM), a selective cyclooxygenase-2 inhibitor. Moreover, we demonstrated that exogenously administered carbacyclin (1 μM, a stable analogue of prostaglandin I 2 ) and/or prostaglandin E 2 (1 μM) caused a significant reduction of reactive oxygen species-induced cell injury, mimicking the effect of trefoil factor 3. In summary, our results indicate that trefoil factor 3 activates cyclooxygenase-2 in intestinal epithelium to produce prostaglandin I 2 and prostaglandin E 2 , which function as survival factors and mediate the cytoprotective action of trefoil factor 3 against oxidant injury.

Original languageEnglish (US)
Pages (from-to)2149-2155
Number of pages7
JournalJournal of Cell Science
Issue number12
StatePublished - Jul 13 2000


  • Intestinal epithelium
  • Oxygen radical species
  • Prostaglandin E
  • Prostaglandin I
  • Trefoil factor

ASJC Scopus subject areas

  • Cell Biology


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