Docosahexaenoic Acid Inhibits Helicobacter pylori-induced STAT3 Phosphorylation through Activation of PPARγ.

Abstract

Docosahexaenoic aicd (DHA), one of the ω-3 polyunsaturated fatty acids, has received considerable attention due to its diverse health beneficial effects. It has been reported that DHA inhibits growth of Helicobacter pylori (H. pylori) in vitro and decreases the colony number in H. pylori-infected mouse stomach in vivo. However, the molecular mechanism underlying the gastroprotective effect of DHA hasnt been clarified. Signal transducer and activator of transcription 3 (STAT3) is a major transcription factor in cancer and activated by H. pylori infection in vitro and in vivo. Therefore, the aim of this study was to investigate the effect of DHA on H. pylori-induced activation of STAT3 signaling in human gastric cancer AGS cells. Pretreatment of AGS cells with DHA significantly reduced the expression, phosphorylation and nuclear translocation of STAT3 induced by H. pylori infection. Notably, DHA activated peroxisome proliferator-activated receptor γ (PPARγ) and induced expression of suppressor of cytokine signaling 3 (SOCS3). siRNA knockdown of PPARγ and SOCS3 abolished the DHA-mediated inhibition of H. pylori-induced STAT3 phosphorylation. DHA also markedly decreased anchorage-independent growth of AGS cells co-cultured with H. pylori. In conclusion, DHA prevents H. pylori-induced STAT3 phosphorylation in a PPARγ/SOCS3-dependent manner.