title: SIRT2 ameliorates lipopolysaccharide-induced inflammation in macrophages.
abstract: BACKGROUND
  SIRT2 is a NAD(+)-dependent deacetylases and associated with numerous processes such as infection, carcinogenesis, DNA damage and cell cycle regulation. However, the role of SIRT2 in inflammatory process in macrophage remains unclear.
  
  
  METHODS
  In the present study, we have evaluated the regulatory effects of SIRT2 in lipopolysaccharide (LPS)-stimulated macrophages isolated from SIRT2 knockout (KO) and wild type (WT) mice or Raw264.7 macrophage cells. As inflammatory parameters, expression of inducible nitric oxide synthase (iNOS), the productions of nitric oxide, reactive oxygen species (ROS) and M1-macrophage-related factors were evaluated. We also examined the effects of SIRT2 on activation of nuclear factor-kappaB (NFκB) signaling.
  
  
  RESULTS
  SIRT2 deficiency inhibits LPS-induced iNOS mRNA and protein expression in bone marrow derived macrophages. SIRT2-siRNA transfection also suppressed LPS-induced iNOS expression in Raw264.7 macrophage cells. Bone marrow derived macrophages isolated from SIRT2 KO mice produced lower nitric oxide and expressed lower levels of M1-macrophage related markers including iNOS and CD86 in response to LPS than WT mice. Decrease of SIRT2 reduced the LPS-induced reactive oxygen species production. Deficiency of SIRT2 resulted in inhibition of NFκB activation through reducing the phosphorylation and degradation of IκBα. The phosphorylation and nuclear translocation of p65 was significantly decreased in SIRT2-deficient macrophages after LPS stimulation.
  
  
  CONCLUSIONS
  Our data suggested that deficiency of SIRT2 ameliorates iNOS, NO expression and reactive oxygen species production with suppressing LPS-induced activation of NFκB in macrophages.
authors.affiliation: Department of Internal Medicine, Chonbuk National University Medical School, Jeonju, Republic of Korea.
authors.forename: Ae Sin
authors.initials: AS
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, Chonbuk National University Medical School, Jeonju, Republic of Korea.
authors.forename: Yu Jin
authors.initials: YJ
authors.lastname: Jung
authors.affiliation: Department of Internal Medicine, Chonbuk National University Medical School, Jeonju, Republic of Korea.
authors.forename: Dal
authors.initials: D
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Chonbuk National University Medical School, Jeonju, Republic of Korea.
authors.forename: Tung
authors.initials: T
authors.lastname: Nguyen-Thanh
authors.affiliation: Department of Internal Medicine, Chonbuk National University Medical School, Jeonju, Republic of Korea; Research Institute of Clinical Medicine of Chonbuk National University, Chonbuk National University Hospital, Jeonju, Republic of Korea.
authors.forename: Kyung Pyo
authors.initials: KP
authors.lastname: Kang
authors.affiliation: Department of Internal Medicine, Chonbuk National University Medical School, Jeonju, Republic of Korea.
authors.forename: Sik
authors.initials: S
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, Chonbuk National University Medical School, Jeonju, Republic of Korea; Research Institute of Clinical Medicine of Chonbuk National University, Chonbuk National University Hospital, Jeonju, Republic of Korea.
authors.forename: Sung Kwang
authors.initials: SK
authors.lastname: Park
authors.affiliation: Department of Internal Medicine, Chonbuk National University Medical School, Jeonju, Republic of Korea; Research Institute of Clinical Medicine of Chonbuk National University, Chonbuk National University Hospital, Jeonju, Republic of Korea. Electronic address: kwon@jbnu.ac.kr.
authors.forename: Won
authors.initials: W
authors.lastname: Kim
mesh_terms: D000818:Animals; D007249:Inflammation / Q000139:chemically induced / Q000517:prevention & control*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D056565:Sirtuin 2 / Q000502:physiology*
chemical_list: D008070:Lipopolysaccharides; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; C418743:Sirt2 protein, mouse; D056565:Sirtuin 2
keywords: Inducible nitric oxide synthase; Macrophage; Nitric oxide; Reactive oxygen species; SIRT2