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Taurine Chloramine Stimulates Efferocytosis through Upregulation of Heme Oxygenase-1 Expression and Production of Carbon Monoxide : Heme Oxygenase-1 (HO-1) 의 발현과 Carbon Monoxide (CO) 의 생산을 통한 Taurine Chloramine 의 Efferocytosis 촉진 효과 기전
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- Authors
- Advisor
- 서영준
- Major
- 의과대학 협동과정 종양생물학전공
- Issue Date
- 2014-02
- Publisher
- 서울대학교 대학원
- Keywords
- TauCl ; Resolution of inflammation ; Effeocytosis ; Heme oxygenase-1 ; Nrf2 ; Carbon monoxide ; Scavenger receptor
- Description
- 학위논문 (석사)-- 서울대학교 대학원 : 협동과정 종양생물학전공, 2014. 2. 서영준.
- Abstract
- During inflammation, taurine chloramine (TauCl) is produced abundantly in activated neutrophils and released to surrounding inflammatory milieu as the activated neutrophils undergo apoptosis. TauCl injected in vivo into the peritoneum of mice undergoing zymosan A-induced peritonitis was found to markedly decrease the number of peritoneal leukocytes and yet increase the blood monocyte infiltration, enhancing resolution of inflammation. Furthermore, when the macrophages obtained from peritoneal exudates were treated with TauCl ex vivo, their ability to phagocytose the apoptotic neutrophils obtained from the same peritoneal exudates was increased. In the murine macrophage-like RAW264.7 cells treated with TauCl, efferocytic activity to phagocytose the apoptotic Jurkat T cells was also enhanced. In these macrophages treated with TauCl, expression of heme oxygenase-1 (HO-1) was increased along with increased nuclear translocation of the nuclear factor E2-related factor 2 (Nrf2). Furthermore, transcriptional expression of scavenger receptors recognizing the phosphatidylserines exposed on the surface of apoptotic cells were increased in these RAW264.7 cells treated with TauCl. Knock-down of HO-1 gene in RAW264.7 cells abolished the TauCl induced activation of efferocytosis, whereas both the overexpression of HO-1 and treatment with carbon monoxide (CO), the product of heme oxygenase, obtained from CO-releasing molecule (CORM) added exogenously increased the efferocytic ability of macrophages. When the macrophages not treated with TauCl were exposed to CORM, transcriptional expression of scavenger receptors was increased. Taken together, our results suggest that TauCl might facilitate resolution of inflammation by increasing the efferocytic activity of macrophages through Nrf2-mediated upregulation of HO-1 expression and overproduction of CO.
- Language
- English
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