Home Bratislava Medical Journal 2016 Bratislava Medical Journal Vol.117, No.6, p.332-339, 2016

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Published Monthly, in English
Founded: 1919
ISSN 0006-9248
(E)ISSN 1336-0345
 

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Bratislava Medical Journal Vol.117, No.6, p.332-339, 2016

Title: Trefoil factor 3 (TFF3) from human breast milk activates PAR-2 receptors, of the intestinal epithelial cells HT-29, regulating cytokines and defensins
Author: G. J. Barrera Roa, G. Sanchez Tortolero

Abstract: Trefoil factors are effector molecules in gastrointestinal tract physiology. Each one improves healing of the gastrointestinal tract. Trefoil factors may be grouped into three classes: the gastric peptides (TFF1), spasmolytic peptide (TFF2) and intestinal trefoil factor (TFF3). Significant amounts of TFF3 are present in human breast milk. Previously, we have reported that trefoil factor 3 isolated from human breast milk produces down regulation of cytokines and promotes human beta defensins expression in intestinal epithelial cells. This study aimed to determine the molecular mechanism involved. Here we showed that the presence of TFF3 strongly correlated with protease activated receptors 2 (PAR-2) activation in human intestinal cells. Intracellular calcium ((Ca2+)i)mobilization was induced by the treatment with: 1) TFF3, 2) synthetic PAR-2 agonist peptide. The co-treatment with a synthetic PAR-2 antagonist peptide and TFF3 eliminates the latter’s effect. Additionally, we demonstrated the existence of interactions among TFF3 and PAR-2 receptors through far Western blot and co-precipitation. Finally, down regulation of PAR-2 by siRNA resulted in a decrease of TFF3 induced intracellular (Ca2+)i mobilization, cytokine regulation and defensins expression. These findings suggest that TFF3 activates intestinal cells through PAR-2 (Fig. 4, Ref. 19).

Keywords: breast milk, trefoil factor family TFF, protease-activated receptor 2 PAR-2, defensins, cytokines
Published online: 13-Jun-2016
Year: 2016, Volume: 117, Issue: 6 Page From: 332, Page To: 339
doi:10.4149/BLL_2016_066


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