| High-fat diet activates pro-inflammatory response in the prostate through association of Stat-3 and NF-κB. | |
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MedLine Citation:
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PMID: 21604287 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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BACKGROUND: 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. METHODS: 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 (EMSA) were conducted to study the association between Stat-3 and NF-κB. RESULTS: C57BL/6 mice fed with HFD showed a significant increase in the plasma levels of IL-1ß, 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. CONCLUSIONS: 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. Prostate © 2011 Wiley-Liss, Inc. |
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Authors:
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Eswar Shankar; Eugene V Vykhovanets; Olena V Vykhovanets; Gregory T Maclennan; Rajesh Singh; Natarajan Bhaskaran; Sanjeev Shukla; Sanjay Gupta |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-5-20 |
Journal Detail:
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Title: The Prostate Volume: - ISSN: 1097-0045 ISO Abbreviation: - Publication Date: 2011 May |
Date Detail:
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Created Date: 2011-5-23 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8101368 Medline TA: Prostate Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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Copyright © 2011 Wiley-Liss, Inc. |
Affiliation:
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Department of Urology, Case Western Reserve University & The Urology Institute, University Hospitals Case Medical Center, Cleveland, Ohio. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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