High-fat diet activates pro-inflammatory response in the prostate through association of Stat-3 and NF-κB.
High-fat diet activates pro-inflammatory response in the prostate through association of Stat-3 and NF-κB.
复制标题
DOI：
10.1002/pros.21425
复制
发表时间：
2012-02
期刊：
影响因子：
2.8
通讯作者：
Gupta, Sanjay
中科院分区：
文献类型：
--
作者：
Shankar, Eswar;Vykhovanets, Eugene V.;Vykhovanets, Olena V.;MacLennan, Gregory T.;Singh, Rajesh;Bhaskaran, Natarajan;Shukla, Sanjeev;Gupta, Sanjay
信号转导子和转录激活子（Signaltransducerandactivatoroftranscription，Stat）-3和核因子-κ B（nuclearfactor-kappaB，NF-κB）是炎症过程中组成性激活的重要信号通路。我们先前报道了高脂饮食（HFD）摄入通过NADPH氧化酶亚基的表达升高引起NF-κB活化诱导前列腺氧化应激。我们试图确定Stat-3是否参与了HFD喂养导致的前列腺中NF-κB的活化，从而导致炎症。C57 BL/6小鼠用常规饮食（RD）或HFD喂养4周和8周。通过多重分析测定血浆细胞因子水平。Western blotting检测前列腺组织中NF-κB、Stat-3、Akt、PDK 1、PKCε及其磷酸化形式的表达沿着进行病理学评价。采用免疫沉淀法和电泳迁移率变动法研究Stat-3与NF-κB的相互作用。与RD对照组相比，喂食HFD的C57 BL/6小鼠在喂食4周和8周后显示出IL-1β、IL-6、IL-17和TNFα的血浆水平显著升高。HFD喂养增加前列腺内IL-6的表达，并引起PKCε和Akt的激活，其上游激酶调节Stat-3和NF-κB。来自喂食HFD的小鼠前列腺的核提取物表现出组成性活化水平的Stat-3和NF-κB/p65。由于HFD喂养，在细胞核中观察到活化形式的Stat-3和NF-κB/p65之间的关联增加，这一发现伴随着前列腺内炎症增加的形态学证据。我们的研究结果表明，HFD激活前列腺中的Stat-3和NF-κB/p65，它们的相互作用与前列腺炎症增加有关。
Signal transducer and activator of transcription (Stat)-3 and nuclear factor-kappa B (NF-κB) are important signaling pathways constitutively activated during inflammation. We previously reported that high-fat diet (HFD) intake induces oxidative stress in the prostate through elevated expression of NADPH oxidase subunits causing NF-κB activation. We sought to determine whether Stat-3 is involved in the activation of NF-κB in the prostate as a result of HFD feeding, leading to inflammation. C57BL/6 mice were either fed with regular diet (RD) or HFD for 4 and 8 weeks. Plasma cytokine levels were determined by multiplex analysis. Western blotting was performed to determine the expression of NF-κB, Stat-3, Akt, PDK1, PKCε and their phosphorylated forms along with pathologic evaluation of the prostate. Immunoprecipitation and electrophoretic mobility shift assay were conducted to study the association between Stat-3 and NF-κB. C57BL/6 mice fed with HFD showed a significant increase in the plasma levels of IL-1β, IL-6, IL-17 and TNFα after 4 and 8 weeks of feeding, compared with RD controls. HFD feeding elevated the intraprostatic expression of IL-6 and caused activation of PKCε and Akt, the upstream kinase regulating Stat-3 and NF-κB. Nuclear extracts from the prostates of mice fed with HFD exhibited constitutively activated levels of Stat-3 and NF-κB/p65. Increased association between the activated forms of Stat-3 and NF-κB/p65 was observed in the nucleus as a result of HFD feeding, a finding that was accompanied by morphologic evidence of increased intraprostatic inflammation. Our findings suggest that HFD activates Stat-3 and NF-κB/p65 in the prostate, and their interaction is associated with increased inflammation in the prostate.
登录
查看更多内容
影响因子：
37.3
作者：
Gorin MA;Pan Q
通讯作者：
Pan Q
影响因子：
4.4
作者：
Mattioli, I;Sebald, A;Schmitz, ML
通讯作者：
Schmitz, ML
影响因子：
50.3
作者：
Lee H;Herrmann A;Deng JH;Kujawski M;Niu G;Li Z;Forman S;Jove R;Pardoll DM;Yu H
通讯作者：
Yu H
影响因子：
4.8
作者：
Sakurai, H;Suzuki, S;Saiki, I
通讯作者：
Saiki, I
影响因子：
3.3
作者：
Greenfield, Jerry R.;Campbell, Lesley V.
通讯作者：
Campbell, Lesley V.