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Docosahexaenoic acid inhibits Helicobacter pylori-induced STAT3 phosphorylation through activation of PPAR gamma

Cited 17 time in Web of Science Cited 16 time in Scopus
Issue Date
2016-06
Citation
Molecular Nutrition and Food Research, Vol.60 No.6, pp.1448-1457
Keywords
DHAH. pyloriPPAR gammaSOCS3STAT3
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's phosphorylation induced by H. pylori infection. DHA also induced nuclear translocation, DNA binding, and transcriptional activities of peroxisome proliferator-activated receptor gamma (PPARy) in AGS cells. Knockdown of PPARy inhibited the transcription of SOCS3 and attenuated the suppressive effect of DHA on phosphorylation of STAT3Tyr(705) induced by H. pylori. The PPARy antagonist bisphenol A diglycidyl ether also mitigated the suppressive effect of DHA on H. pylori-induced phosphorylation of STAT3Tyr(705). 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 PPARy/SOCS3-dependent manner.
ISSN
1613-4125
URI
https://hdl.handle.net/10371/172831
DOI
https://doi.org/10.1002/mnfr.201600009
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Graduate School of Convergence Science and Technology (융합과학기술대학원)Dept. of Molecular and Biopharmaceutical Sciences (분자의학 및 바이오제약학과)Journal Papers (저널논문_분자의학 및 바이오제약학과)
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