Docosahexaenoic acid inhibits Helicobacter pylori-induced STAT3 phosphorylation through activation of PPARgamma.
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Ji HG, Piao JY, Kim SJ, Kim DH, Lee HN, Na HK, Surh YJ
Docosahexaenoic acid inhibits Helicobacter pylori-induced STAT3 phosphorylation through activation of PPARgamma.
Mol Nutr Food Res. 2016 Jun;60(6):1448-57. doi: 10.1002/mnfr.201600009. Epub 2016 May 9.
- PubMed ID
- 27079734 [ View in PubMed]
- 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 (PPARgamma) in AGS cells. Knockdown of PPARgamma inhibited the transcription of SOCS3 and attenuated the suppressive effect of DHA on phosphorylation of STAT3(Tyr705) induced by H. pylori. The PPARgamma 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 PPARgamma/SOCS3-dependent manner.
DrugBank Data that Cites this Article
- Drug Targets
Drug Target Kind Organism Pharmacological Action Actions Doconexent Myc proto-oncogene protein Protein Humans UnknownInhibitorDetails Doconexent Peroxisome proliferator-activated receptor alpha Protein Humans YesActivatorDetails Doconexent Peroxisome proliferator-activated receptor gamma Protein Humans YesActivatorDetails