Sirtuin 2 Regulates Microvascular Inflammation during Sepsis

Journal of Immunology Research
Nancy L BuechlerVidula Vachharajani

Abstract

Objective. Sepsis and septic shock, the leading causes of death in noncoronary intensive care units, kill more than 200,000/year in the US alone. Circulating cell-endothelial cell interactions are the rate determining factor in sepsis inflammation. Sirtuin, a seven-member family of proteins (SIRT1-7), epigenetically controls inflammation. We have studied the roles of SIRTs 1, 3, and 6 in sepsis previously. In this project, we studied the role of SIRT2 on sepsis-related inflammation. Methods. Sepsis was induced in C57Bl/6 (WT), SIRT2 knockout (SIRT2KO), and SIRT2 overexpressing (SIRT2KI) mice by cecal ligation and puncture (CLP). We studied leukocyte/platelet adhesion using intravital microscopy and E-selectin/ICAM-1 adhesion molecule expression in the small intestine with immunohistochemistry (IHC) six hours post-CLP/sham surgery. We also studied 7-day survival rates in WT, SIRT2KO, and SIRT2KI sepsis mice. Results. Compared to WT mice, SIRT2KO mice show exaggeration while SIRT2KI mice show attenuation of cellular adhesion with sepsis in the small intestine. We also show that the small intestinal E-selectin and ICAM-1 expressions increased in SIRT2KO and decreased in SIRT2KI mice versus those in WT sepsis mice. We show that the...Continue Reading

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Citations

Mar 17, 2020·Expert Opinion on Therapeutic Targets·Vidula Vachharajani, Charles E McCall
Jun 10, 2020·Journal of Cellular and Molecular Medicine·Kai SunShaoping Ji
Apr 25, 2019·International Journal of Molecular Medicine·Xiaojing FanHui Deng
Dec 12, 2018·Critical Care Research and Practice·Lulan LiZhenhua Zeng
Sep 12, 2018·Inflammation·Xianfeng WangVidula Vachharajani
Sep 16, 2018·International Journal of Molecular Sciences·Xianfeng WangVidula Vachharajani
Jan 23, 2019·JCI Insight·Yong Gyu LeeMegan N Ballinger
Apr 25, 2018·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·Sören SwyterManfred Jung
Sep 11, 2019·Ageing Research Reviews·Yan WangLili Cui
Mar 7, 2021·Biomolecules·Yuqing ZhangAndrew Keith Davey
May 26, 2021·European Journal of Pharmacology·Zhe ChengJianghong Yan

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Methods Mentioned

BETA
acetylation
transgenics
intravital microscopy
lavage

Software Mentioned

SAS
Statview
Graph Pad Prism
Graph Pad

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