title: Taurine Chloramine Stimulates Efferocytosis Through Upregulation of Nrf2-Mediated Heme Oxygenase-1 Expression in Murine Macrophages: Possible Involvement of Carbon Monoxide.
abstract: OBJECTIVE
  To examine the pro-resolving effects of taurine chloramine (TauCl).
  
  
  RESULTS
  TauCl injected into the peritoneum of mice enhanced the resolution of zymosan A-induced peritonitis. Furthermore, when the macrophages obtained from peritoneal exudates were treated with TauCl, their efferocytic ability was elevated. In the murine macrophage-like RAW264.7 cells exposed to TauCl, the proportion of macrophages engulfing the apoptotic neutrophils was also increased. In these macrophages treated with TauCl, expression of heme oxygenase-1 (HO-1) was elevated along with increased nuclear translocation of the nuclear factor E2-related factor 2 (Nrf2). TauCl binds directly to Kelch-like ECH association protein 1 (Keap1), which appears to retard the Keap1-driven degradation of Nrf2. This results in stabilization and enhanced nuclear translocation of Nrf2 and upregulation of HO-1 expression. TauCl, when treated to peritoneal macrophages isolated from either Nrf2 or HO-1 wild-type mice, stimulated efferocytosis (phagocytic engulfment of apoptotic neutrophils by macrophages), but not in the macrophages from Nrf2 or HO-1 knockout mice. Furthermore, transcriptional expression of some scavenger receptors recognizing the phosphatidylserines exposed on the surface of apoptotic cells was increased in RAW264.7 cells treated with TauCl. Pharmacologic inhibition of HO-1 activity or knockdown of HO-1 gene in RAW264.7 cells abolished the TauCl-induced efferocytosis, whereas both overexpression of HO-1 and treatment with carbon monoxide (CO), the product of HO, potentiated the efferocytic activity of macrophages.
  
  
  METHODS
  This work provides the first evidence that TauCl stimulates efferocytosis by macrophages. The results of this study suggest the therapeutic potential of TauCl in the management of inflammatory disorders.
  
  
  CONCLUSIONS
  TauCl can facilitate resolution of inflammation by increasing the efferocytic activity of macrophages through Nrf2-mediated HO-1 upregulation and subsequent production of CO.
authors: 1 Tumor Microenvironment Global Core Research Center and Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University , Seoul, Republic of Korea.
authors: Wonki
authors: W
authors: Kim
authors: 1 Tumor Microenvironment Global Core Research Center and Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University , Seoul, Republic of Korea.
authors: Hoon-Ui
authors: HU
authors: Kim
authors: 1 Tumor Microenvironment Global Core Research Center and Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University , Seoul, Republic of Korea.
authors: Ha-Na
authors: HN
authors: Lee
authors: 1 Tumor Microenvironment Global Core Research Center and Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University , Seoul, Republic of Korea.
authors: Seung Hyeon
authors: SH
authors: Kim
authors: 2 Department of Pharmacology and Toxicology, College of Medicine, Inha University , Incheon, Republic of Korea.
authors: Chaekyun
authors: C
authors: Kim
authors: 2 Department of Pharmacology and Toxicology, College of Medicine, Inha University , Incheon, Republic of Korea.
authors: Young-Nam
authors: YN
authors: Cha
authors: 3 Meta-Inflammation Basic Research Laboratory, School of Biological Sciences, University of Ulsan , Ulsan, Republic of Korea.
authors: Yeonsoo
authors: Y
authors: Joe
authors: 3 Meta-Inflammation Basic Research Laboratory, School of Biological Sciences, University of Ulsan , Ulsan, Republic of Korea.
authors: Hun Taeg
authors: HT
authors: Chung
authors: 1 Tumor Microenvironment Global Core Research Center and Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University , Seoul, Republic of Korea.
authors: Jaebong
authors: J
authors: Jang
authors: 1 Tumor Microenvironment Global Core Research Center and Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University , Seoul, Republic of Korea.
authors: Kyeojin
authors: K
authors: Kim
authors: 1 Tumor Microenvironment Global Core Research Center and Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University , Seoul, Republic of Korea.
authors: Young-Ger
authors: YG
authors: Suh
authors: 4 KIRAMS Radiation Biobank, Korea Institute of Radiological & Medical Sciences , Seoul, Republic of Korea.
authors: Hyeon-Ok
authors: HO
authors: Jin
authors: 4 KIRAMS Radiation Biobank, Korea Institute of Radiological & Medical Sciences , Seoul, Republic of Korea.
authors: Jin Kyung
authors: JK
authors: Lee
authors: 1 Tumor Microenvironment Global Core Research Center and Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University , Seoul, Republic of Korea.|5 Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science, Seoul National University , Seoul, Republic of Korea.|6 Cancer Research Institute, Seoul National University , Seoul, Republic of Korea.
authors: Young-Joon
authors: YJ
authors: Surh
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000818:Animals; D002248:Carbon Monoxide / Q000378:metabolism*; D003598:Cytoskeletal Proteins / Q000378:metabolism; D004195:Disease Models, Animal; D051547:Heme Oxygenase-1 / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D019169:Jurkat Cells; D000072019:Kelch-Like ECH-Associated Protein 1; D008264:Macrophages / Q000378:metabolism*; D017737:Macrophages, Peritoneal / Q000378:metabolism*; D051379:Mice; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D010587:Phagocytosis / Q000187:drug effects*; D013654:Taurine / Q000031:analogs & derivatives* / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects*; D015054:Zymosan / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D003598:Cytoskeletal Proteins; C117301:Keap1 protein, mouse; D000072019:Kelch-Like ECH-Associated Protein 1; D051267:NF-E2-Related Factor 2; C495636:Nfe2l2 protein, mouse; D013654:Taurine; C043410:N-chlorotaurine; D002248:Carbon Monoxide; D015054:Zymosan; D051547:Heme Oxygenase-1