Docosahexaenoic acid inhibits Helicobacter pylori‐induced STAT3 phosphorylation through activation of PPARγ. Issue 6 (9th May 2016)

• Record Type: Journal Article
• Authors: Ji, Hyeon‐Geun; Piao, Juan‐Yu; Kim, Su‐Jung; Kim, Do‐Hee; Lee, Ha‐Na; Na, Hye‐Kyung; Surh, Young‐Joon
• Is Part Of: Molecular nutrition & food research. Volume 60:Issue 6(2016)
• Page Start: 1448
• Page End: 1457
• Publication Date: 2016-05-09
• Subjects: DHA -- H. pylori -- PPARγ -- SOCS3 -- STAT3; Food -- Biotechnology -- Periodicals; Food -- Microbiology -- Periodicals; Nutrition -- Periodicals; Food -- Toxicology -- Periodicals; Nutrition -- Periodicals; Food Microbiology -- Periodicals; Food Technology -- Periodicals; Molecular Biology -- Periodicals; 664.0705
• DOI: 10.1002/mnfr.201600009
• Languages: English
• ISSNs: 1613-4125

Abstract

Abstract : The present study demonstrates that docosahexaenoic acid (DHA) suppresses the activation of signal transducer and activator of transcription 3 (STAT3) in human gastric cancer AGS cells infected with Helicobacter pylori . DHA treatment activates peroxisome proliferator‐activated receptor gamma (PPARγ) which, in turn, induces the expression of suppressor of cytokine signaling 3 (SOCS3). The upregulated SOCS3 then inhibits H. pylori ‐induced phosphorylation and nuclear translocation of STAT3, leading to suppression of its target gene (c‐ Myc ) expression and consequently growth of AGS cells. 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.