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Mol Nutr Food Res. 2016 Jun;60(6):1448-57. doi: 10.1002/mnfr.201600009. Epub 2016 May 9.

Docosahexaenoic acid inhibits Helicobacter pylori-induced STAT3 phosphorylation through activation of PPARγ.

Author information

1
Cancer Research Institute, Seoul National University, Seoul, South Korea.
2
Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul, South Korea.
3
Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Sciences, Seoul, South Korea.
4
Department of Food and Nutrition, College of Human Ecology, Sungshin Women's University, Seoul, South Korea.

Abstract

SCOPE:

The health beneficial effects of docosahexaenoic acid (DHA) have been attributed to its anti-inflammatory properties. However, the molecular mechanism underlying anti-inflammatory effects of DHA remains largely elusive.

METHODS AND RESULTS:

In the present study, DHA was found to suppress the phosphorylation and nuclear translocation of signal transducer and activator of transcription 3 (STAT3) induced by Helicobacter pylori infection in human gastric cancer AGS cells. Notably, DHA induced expression of suppressor of cytokine signaling 3 (SOCS3), a negative regulator of STAT3. Knockdown of SOCS3 abolished the suppressive effect of DHA on STAT3(Tyr705) phosphorylation induced by H. pylori infection. DHA also induced nuclear translocation, DNA binding, and transcriptional activities of peroxisome proliferator-activated receptor gamma (PPARγ) in AGS cells. Knockdown of PPARγ inhibited the transcription of SOCS3 and attenuated the suppressive effect of DHA on phosphorylation of STAT3(Tyr705) induced by H. pylori. The PPARγ antagonist bisphenol A diglycidyl ether also mitigated the suppressive effect of DHA on H. pylori-induced phosphorylation of STAT3(Tyr705) . In addition, DHA inhibited the expression of c-Myc, which was attenuated in the AGS cells harboring SOCS3 specific siRNA. DHA also markedly decreased anchorage-independent growth of AGS cells infected by H. pylori.

CONCLUSION:

DHA inhibits H. pylori-induced STAT3 phosphorylation in a PPARγ/SOCS3-dependent manner.

KEYWORDS:

DHA; H. pylori; PPARγ; SOCS3; STAT3

PMID:
27079734
DOI:
10.1002/mnfr.201600009
[Indexed for MEDLINE]

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