Wonki Kim1, Hoon-Ui Kim1, Ha-Na Lee1, Seung Hyeon Kim1, Chaekyun Kim2, Young-Nam Cha2, Yeonsoo Joe3, Hun Taeg Chung3, Jaebong Jang1, Kyeojin Kim1, Young-Ger Suh1, Hyeon-Ok Jin4, Jin Kyung Lee4, Young-Joon Surh1,5,6. 1. 1 Tumor Microenvironment Global Core Research Center and Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University , Seoul, Republic of Korea. 2. 2 Department of Pharmacology and Toxicology, College of Medicine, Inha University , Incheon, Republic of Korea. 3. 3 Meta-Inflammation Basic Research Laboratory, School of Biological Sciences, University of Ulsan , Ulsan, Republic of Korea. 4. 4 KIRAMS Radiation Biobank, Korea Institute of Radiological & Medical Sciences , Seoul, Republic of Korea. 5. 5 Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science, Seoul National University , Seoul, Republic of Korea. 6. 6 Cancer Research Institute, Seoul National University , Seoul, Republic of Korea.
Abstract
AIMS: 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. INNOVATION: 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. CONCLUSION: TauCl can facilitate resolution of inflammation by increasing the efferocytic activity of macrophages through Nrf2-mediated HO-1 upregulation and subsequent production of CO.
AIMS: 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. INNOVATION: 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. CONCLUSION: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: Gerard L Bannenberg; Nan Chiang; Amiram Ariel; Makoto Arita; Eric Tjonahen; Katherine H Gotlinger; Song Hong; Charles N Serhan Journal: J Immunol Date: 2005-04-01 Impact factor: 5.422
Authors: Janusz Marcinkiewicz; Markus Nagl; Anthony Kyriakopoulos; Maria Walczewska; Magdalena Skóra; Paulina Skalska Journal: Adv Exp Med Biol Date: 2022 Impact factor: 3.650
Authors: Shirley Dehn; Matthew DeBerge; Xin-Yi Yeap; Laurent Yvan-Charvet; Deyu Fang; Holger K Eltzschig; Stephen D Miller; Edward B Thorp Journal: J Immunol Date: 2016-09-26 Impact factor: 5.422