Myeloid deletion of SIRT1 induces inflammatory signaling in response to environmental stress.

Molecular and Cellular Biology
Thaddeus T SchugXiaoling Li

Abstract

Macrophage activation and infiltration into resident tissues is known to mediate local inflammation and is a hallmark feature of metabolic syndrome. Members of the sirtuin family of proteins regulate numerous physiological processes, including those involved in nutrient regulation and the promotion of longevity. However, the important role that SIRT1, the leading sirtuin family member, plays in immune response remains unclear. In this study, we demonstrate that SIRT1 modulates the acetylation status of the RelA/p65 subunit of NF-κB and thus plays a pivotal role in regulating the inflammatory, immune, and apoptotic responses in mammals. Using a myeloid cell-specific SIRT1 knockout (Mac-SIRT1 KO) mouse model, we show that ablation of SIRT1 in macrophages renders NF-κB hyperacetylated, resulting in increased transcriptional activation of proinflammatory target genes. Consistent with increased proinflammatory gene expression, Mac-SIRT1 KO mice challenged with a high-fat diet display high levels of activated macrophages in liver and adipose tissue, predisposing the animals to development of systemic insulin resistance and metabolic derangement. In summary, we report that SIRT1, in macrophages, functions to inhibit NF-κB-mediated tra...Continue Reading

References

Feb 5, 2000·The Journal of Immunology : Official Journal of the American Association of Immunologists·J A NickG S Worthen
May 17, 2000·Proceedings of the National Academy of Sciences of the United States of America·J LandryR Sternglanz
Jun 7, 2000·Proceedings of the National Academy of Sciences of the United States of America·J S SmithJ D Boeke
Jun 30, 2000·Biochemical and Biophysical Research Communications·R A Frye
May 2, 2002·Cell·Sankar Ghosh, Michael Karin
Jul 5, 2002·Clinical Microbiology Reviews·Jorge Caamaño, Christopher A Hunter
Nov 7, 2002·The Journal of Biological Chemistry·Rosemary KiernanMonsef Benkirane
Nov 29, 2002·The EMBO Journal·Lin-feng ChenWarner C Greene
Jan 4, 2003·Nature Reviews. Immunology·Siamon Gordon
Sep 10, 2003·Proceedings of the National Academy of Sciences of the United States of America·Hwei-Ling ChengKatrin F Chua
Dec 18, 2003·The Journal of Clinical Investigation·Stuart P WeisbergAnthony W Ferrante
Dec 18, 2003·The Journal of Clinical Investigation·Haiyan XuHong Chen
Feb 26, 2004·Cell·Maria Carla MottaLeonard Guarente
Dec 29, 2004·Physiology & Behavior·Stephen C WoodsRandy J Seeley
Jul 4, 2006·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Carl-Magnus BäckesjöLars-Arne Haldosén
Jul 11, 2006·The Journal of Clinical Investigation·Steven E ShoelsonAllison B Goldfine
Oct 21, 2006·The Journal of Clinical Investigation·Hang ShiJeffrey S Flier
Oct 21, 2006·The Journal of Clinical Investigation·Tatiana KisselevaChristian Schindler
Oct 31, 2006·Oncogene·M S HaydenS Ghosh
Dec 15, 2006·Nature·Gökhan S Hotamisligil
Jan 9, 2007·Trends in Molecular Medicine·Danica Chen, Leonard Guarente
Feb 23, 2008·The Journal of Immunology : Official Journal of the American Association of Immunologists·Kathleen SmoakMichael B Fessler
Jul 5, 2008·Proceedings of the National Academy of Sciences of the United States of America·Paul T PflugerMatthias H Tschöp
Dec 24, 2008·Molecular and Cellular Biology·Takeshi YoshizakiJerrold M Olefsky
Mar 21, 2009·American Journal of Physiology. Gastrointestinal and Liver Physiology·Zheng ShenMin You
Dec 10, 2009·American Journal of Physiology. Endocrinology and Metabolism·Takeshi YoshizakiJerrold M Olefsky

❮ Previous
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Citations

Mar 25, 2011·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Antero SalminenKai Kaarniranta
Nov 23, 2011·Immunology and Cell Biology·Sinyi KongDeyu Fang
Nov 26, 2010·Nature Reviews. Cancer·Daniel Herranz, Manuel Serrano
Jan 18, 2012·Nature Reviews. Endocrinology·Angeliki Chalkiadaki, Leonard Guarente
Jan 6, 2012·Proceedings of the National Academy of Sciences of the United States of America·Beixue GaoDeyu Fang
Apr 7, 2011·The Journal of Biological Chemistry·Michel BernierRafael de Cabo
Aug 16, 2012·The Journal of Biological Chemistry·Yolanda AlvarezMariano Sánchez Crespo
Oct 23, 2012·The Journal of Biological Chemistry·Carlos SebastiánRaul Mostoslavsky
Sep 6, 2011·Nucleic Acids Research·Xiaoyan WuYong Xu
Oct 19, 2011·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Aparna PurushothamXiaoling Li
Nov 26, 2010·Journal of Neuro-ophthalmology : the Official Journal of the North American Neuro-Ophthalmology Society·Lynn K Gordon, Jeffrey L Bennett
Apr 14, 2012·Genome Research·Roberto FerrariSiavash K Kurdistani
Jan 5, 2011·Molecular and Cellular Biology·Ulf H BeierWayne W Hancock
May 2, 2012·The Journal of Clinical Investigation·Hongwei YaoIrfan Rahman
May 10, 2011·Cell Communication and Signaling : CCS·Shahedur Rahman, Rezuanul Islam
May 27, 2011·International Journal of Biological Sciences·Xiaoling Li, Nevzat Kazgan
Oct 29, 2014·The Journal of Endocrinology·Sun-O KaByung-Hyun Park
Dec 20, 2014·Journal of Obstetrics and Gynaecology : the Journal of the Institute of Obstetrics and Gynaecology·Emel Kiyak CaglayanAyla Aktulay
Sep 1, 2012·Drug and Chemical Toxicology·Jun XieLi Zhang
Jan 24, 2015·Diabetes·Salmaan Ahmed KhanDouglas G Mashek
Nov 2, 2015·Advances in Medical Sciences·Mateusz Wątroba, Dariusz Szukiewicz
Mar 3, 2015·Proceedings of the National Academy of Sciences of the United States of America·Guangwei LiuRuifu Yang
Jul 24, 2013·Drug Discovery Today. Disease Mechanisms·Joyce V LeeKathryn E Wellen
Jul 24, 2013·Journal of Genetics and Genomics = Yi Chuan Xue Bao·Sinyi KongDeyu Fang
Mar 29, 2013·The Journal of Thoracic and Cardiovascular Surgery·Hirotsugu KurobeTetsuya Kitagawa
Oct 27, 2012·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Jun XieLi Zhang
Sep 22, 2012·Biochemical and Biophysical Research Communications·Ai Takeda-WatanabeDaisuke Koya
Sep 4, 2012·Pharmacology & Therapeutics·Yu WangPaul M Vanhoutte
Jul 4, 2012·Molecular and Cellular Endocrinology·Hayley M O'NeillGregory R Steinberg
Dec 14, 2011·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Hongmei YuanLi Zhang
Jul 30, 2011·Current Opinion in Immunology·Ulf H BeierWayne W Hancock
Oct 26, 2010·Trends in Molecular Medicine·Matthew P GillumGerald I Shulman
Mar 8, 2016·The Canadian Journal of Cardiology·Yujiro Kida, Michael S Goligorsky
Sep 26, 2015·Brain Research·Ana Karolina Santana NunesChristina Alves Peixoto
Apr 17, 2016·Kidney International·Matthew H LevineUlf H Beier

❮ Previous
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