한빛사논문
- 조회1,227
Kyung Soo Hong1, June Hong Ahn1, Jong Geol Jang1, Jong Ho Lee2, Hong Nam Kim3,4, Dongha Kim5 and Wonhwa Lee6
1Division of Pulmonology and Allergy, Department of Internal Medicine, College of Medicine, Yeungnam University and Regional Center for Respiratory Diseases, Yeungnam University Medical Center, Daegu 42415, Republic of Korea; 2Department of Laboratory Medicine, College of Medicine, Yeungnam University, Yeungnam University Medical Center, Daegu 42415, Republic of Korea; 3Brain Science Institute, Korea Institute of Science and Technology (KIST), Seoul 02792, Republic of Korea; 4Division of Bio-Medical Science and Technology, KIST School, Korea University of Science and Technology (UST), Seoul 02792, Republic of Korea; 5Department of Anatomy, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea and 6Aging Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 34141, Republic of Korea
These authors contributed equally: Kyung Soo Hong, June Hong Ahn, Jong Geol Jang
Correspondence: Hong Nam Kim, Dongha Kim, Wonhwa Lee
Abstract
Since the COVID-19 demonstrated a remarkable transmission speed and a high mortality risk, COVID-19 is currently declared as a pandemic by the World Health Organization. This is the first time that the WHO has declared a pandemic since H1N1 in 2009. As of 6 September 2020, the total number of COVID-19 patients is 26,763,217 (876,616 deaths), and it continues to rise (https://covid19.who.int/). In spite of the urgent demand for the vaccines and therapeutics, global efforts are primarily focused on the utilization of the existing anti-viral drugs, such as remdesivir, hydroxychloroquine, and dexamethasone, to relieve the symptoms due to the limited development of renovative therapeutics. Therefore, more fundamental solutions are urgently needed to overcome the threat of the COVID-19. The deterioration of the COVID-19 patients with acute respiratory distress syndrome (ARDS) and sepsis are mainly caused by the cytokine storm, the overproduced cytokines by immune cells. Previous studies indicated that the infection does cause the cytokine storm and subsequently ARDS, and may lead to mortality.1 Therefore, the suppression of the cytokines and subsequent ARDS is important to increase survival rate through the regulation of cytokine gene expression.2 Although NF-κB signaling is known to regulate the cytokine storm, direct targeting of NF-κB is not beneficial since the p65 is readily hyperactivated in COVID-19 patients. Here, we applied a mechanism by which previously reported phosphorylated lysine-specific demethylase 1 (LSD1) stabilizes NF-κB p65 to control the expression of pro-inflammatory cytokine genes.3 We found that pro-inflammatory cytokines were significantly reduced when severe COVID-19 patients’ peripheral blood mononuclear cells (PBMCs) were treated in-vitro with Go6976 (inhibitor of LSD1 phosphorylation) or GSK-LSD1 (inhibitor of LSD1 activity). Therefore, this study suggests the GSK-LSD1 as a therapeutic agent for severe COVID-19 patients that are difficult to treat by directly targeting NF-κB.
논문정보
- Letter
- 2020년 11월 (BRIC 등록일 2020-11-20)
- 국내 연구진
- 바이오·의료융합 > 바이오센싱 및 나노바이오물질
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