[논문]Lung-selective 25-hydroxycholesterol nanotherapeutics as a suppressor of COVID-19-associated cytokine storm

Kim, Hyelim; Lee, Han Sol; Ahn, June Hong; Hong, Kyung Soo; Jang, Jong Geol; An, Jiseon; Mun, Yong-Hyeon; Yoo, So-Yeol; Choi, Yoon Jung; Yun, Mi-Young; Song, Gyu Yong; Joo, Jinmyoung; Na, Dong Hee; Kim, Hong Nam; Park, Hee Ho; Lee, Jae-Young; Lee, Wonhwa

doi:10.1016/j.nantod.2021.101149

[해외논문] Lung-selective 25-hydroxycholesterol nanotherapeutics as a suppressor of COVID-19-associated cytokine storm 원문보기

Nano today, v.38, 2021년, pp.101149 -

Kim, Hyelim (College of Pharmacy, Chungnam National University) , Lee, Han Sol (College of Pharmacy, Chungnam National University) , Ahn, June Hong (Division of Pulmonology and Allergy, Department of Internal Medicine, College of Medicine, Yeungnam University and Regional Center for Respiratory Diseases, Yeungnam University Medical Center) , Hong, Kyung Soo (Division of Pulmonology and Allergy, Department of Internal Medicine, College of Medicine, Yeungnam University and Regional Center for Respiratory Diseases, Yeungnam University Medical Center) , Jang, Jong Geol (Division of Pulmonology and Allergy, Department of Internal Medicine, College of Medicine, Yeungnam University and Regional Center for Respiratory Diseases, Yeungnam University Medical Center) , An, Jiseon (College of Pharmacy, Chungnam National University) , Mun, Yong-Hyeon (College of Pharmacy, Chungnam National U) , Yoo, So-Yeol , Choi, Yoon Jung , Yun, Mi-Young , Song, Gyu Yong , Joo, Jinmyoung , Na, Dong Hee , Kim, Hong Nam , Park, Hee Ho , Lee, Jae-Young , Lee, Wonhwa

Abstract ▼ AI-Helper

Abstract In response to the coronavirus disease-19 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), global efforts are focused on the development of new therapeutic interventions. For the treatment of COVID-19, selective lung-localizing strategies hold tremendous potential, as SARS-CoV-2 invades the lung via ACE2 receptors and causes severe pneumonia. Similarly, recent reports have shown the association of COVID-19 with decreased 25-hydroxycholesterol (25-HC) and increased cytokine levels. This mechanism, which involves the activation of inflammatory NF-κB- and SREBP2-mediated inflammasome signaling pathways, is believed to play a crucial role in COVID-19 pathogenesis, inducing acute respiratory distress syndrome (ARDS) and sepsis. To resolve those clinical conditions observed in severe SARS-CoV-2 patients, we report 25-HC and didodecyldimethylammonium bromide (DDAB) nanovesicles (25-HC@DDAB) as a COVID-19 drug candidate for the restoration of intracellular cholesterol level and suppression of cytokine storm. Our data demonstrate that 25-HC@DDAB can selectively accumulate the lung tissues and effectively downregulate NF-κB and SREBP2 signaling pathways in COVID-19 patient-derived PBMCs, reducing inflammatory cytokine levels. Altogether, our findings suggest that 25-HC@DDAB is a promising candidate for the treatment of symptoms associated with severe COVID-19 patients, such as decreased cholesterol level and cytokine storm. Highlights 25-HC and DDAB nanovesicles (25-HC@DDAB) restore cholesterol levels and effectively suppress cytokine storms. Intravenously administered 25-HC@DDAB exhibits preferential lung tropism and accumulation with high efficiency. 25-HC@DDAB can downregulate NF-κB and SREBP2 signaling pathways in COVID-19 patients' PBMCs, reducing inflammatory cytokine levels. Graphical Abstract [DISPLAY OMISSION]

Keyword

참고문헌 (46)

1 Le T.T. Andreadakis Z. Kumar A. Roman R.G. Tollefsen S. Saville M. Mayhew S. Evolution of the COVID-19 vaccine development landscape Nat. Rev. Drug Discov. 19 2020 667 668 32887942
2 Ge Y. Tian T. Huang S. Wan F. Li J. Li S. Yang H. Hong L. Wu N. Yuan E. Cheng L. Lei Y. Shu H. Feng X. Jiang Z. Chi Y. Guo X. Cui L. Xiao L. Li Z. Yang C. Miao Z. Tang H. Chen L. Zeng H. Zhao D. Zhu F. Shen X. Zeng J. bioRxiv 2020 2020.2003.2011.986836
3 Cao X. COVID-19: immunopathology and its implications for therapy Nat. Rev. Immunol. 20 2020 269 270 32273594

상세보기
4 Tay M.Z. Poh C.M. Rénia L. MacAry P.A. Ng L.F. Nat. Rev. Immunol. 2020 1 12 31792373
5 Hadjadj J. Yatim N. Barnabei L. Corneau A. Boussier J. Smith N. Pere H. Charbit B. Bondet V. Chenevier-Gobeaux C. Breillat P. Carlier N. Gauzit R. Morbieu C. Pene F. Marin N. Roche N. Szwebel T.A. Merkling S.H. Treluyer J.M. Veyer D. Mouthon L. Blanc C. Tharaux P.L. Rozenberg F. Fischer A. Duffy D. Rieux-Laucat F. Kerneis S. Terrier B. Impaired type I interferon activity and inflammatory responses in severe COVID-19 patients Science 369 2020 718 724 32661059

상세보기
6 McDonald J.G. Russell D.W. Editorial: 25-hydroxycholesterol: a new life in immunology J. Leukoc. Biol. 88 2010 1071 1072 21123296

상세보기
7 Russell D.W. The enzymes, regulation, and genetics of bile acid synthesis Annu. Rev. Biochem. 72 2003 137 174 12543708

상세보기
8 Xiao H. Lu M. Lin T.Y. Chen Z. Chen G. Wang W.C. Marin T. Shentu T.P. Wen L. Gongol B. Sun W. Liang X. Chen J. Huang H.D. Pedra J.H. Johnson D.A. Shyy J.Y. Sterol regulatory element binding protein 2 activation of NLRP3 inflammasome in endothelium mediates hemodynamic-induced atherosclerosis susceptibility Circulation 128 2013 632 642 23838163

상세보기
9 Reboldi A. Dang E.V. McDonald J.G. Liang G. Russell D.W. Cyster J.G. 25-Hydroxycholesterol suppresses interleukin-1–driven inflammation downstream of type I interferon Science 345 2014 679 684 25104388

상세보기
10 Jacobs D.R. Jr. Hebert B. Schreiner P.J. Sidney S. Iribarren C. Hulley S. Reduced cholesterol is associated with recent minor illness The CARDIA study Am. J. Epidemiol. 146 1997 558 564 9326433
11 Beisel W.R. Cancer Res. 41 1981 3797 3798 7020936

상세보기
12 Beisel W.R. Fiser R.H. Jr. Lipid metabolism during infectious illness Am. J. Clin. Nutr. 23 1970 1069 1079 4994183

상세보기
13 Alvarez C. Ramos A. Lipids, lipoproteins, and apoproteins in serum during infection Clin. Chem. 32 1986 142 145 3940695

상세보기
14 Lees R.S. Fiser R.H. Jr. Beisel W.R. Bartelloni P.J. Effects of an experimental viral infection on plasma lipid and lipoprotein metabolism Metabolism 21 1972 825 833 4626894

상세보기
15 Sammalkorpi K. Valtonen V. Kerttula Y. Nikkila E. Taskinen M.R. Changes in serum lipoprotein pattern induced by acute infections Metabolism 37 1988 859 865 3419323

상세보기
16 Ettinger W.H. Jr. Harris T. Verdery R.B. Tracy R. Kouba E. Evidence for inflammation as a cause of hypocholesterolemia in older people J. Am. Geriatr. Soc. 43 1995 264 266 7884115

상세보기
17 Harris H.W. Grunfeld C. Feingold K.R. Rapp J.H. Human very low density lipoproteins and chylomicrons can protect against endotoxin-induced death in mice J. Clin. Investig. 86 1990 696 702 2394827
18 Harris H.W. Grunfeld C. Feingold K.R. Read T.E. Kane J.P. Jones A.L. Eichbaum E.B. Bland G.F. Rapp J.H. Chylomicrons alter the fate of endotoxin, decreasing tumor necrosis factor release and preventing death J. Clin. Investig. 91 1993 1028 1034 8450032
19 Zhang Y. Song Z. Wang M. Lan M. Zhang K. Jiang P. Li Y. Bai J. Wang X. Cholesterol 25-hydroxylase negatively regulates porcine intestinal coronavirus replication by the production of 25-hydroxycholesterol Vet. Microbiol. 231 2019 129 138 30955800

상세보기
20 Wu J.T. Leung K. Bushman M. Kishore N. Niehus R. de Salazar P.M. Cowling B.J. Lipsitch M. Leung G.M. Estimating clinical severity of COVID-19 from the transmission dynamics in Wuhan, China Nat. Med. 26 2020 506 510 32284616

상세보기
21 Li G. De Clercq E. Therapeutic options for the 2019 novel coronavirus (2019-nCoV) Nat. Rev. Drug Discov. 19 2020 149 150 32127666
22 Cheng Q. Wei T. Farbiak L. Johnson L.T. Dilliard S.A. Siegwart D.J. Selective organ targeting (SORT) nanoparticles for tissue-specific mRNA delivery and CRISPR–Cas gene editing Nat. Nanotechnol. 15 2020 313 320 32251383

상세보기
23 Hattori Y. Nakamura A. Arai S. Kawano K. Maitani Y. Yonemochi E. siRNA delivery to lung-metastasized tumor by systemic injection with cationic liposomes J. Liposome Res. 25 2015 279 286 25543847

상세보기
24 Kusumoto K.-i Ishikawa T. Didodecyldimethylammonium bromide (DDAB) induces caspase-mediated apoptosis in human leukemia HL-60 cells J. Control. Release 147 2010 246 252 20674638

상세보기
25 Li P. Zhang L. Ai K. Li D. Liu X. Wang E. Coating didodecyldimethylammonium bromide onto Au nanoparticles increases the stability of its complex with DNA J. Control. Release 129 2008 128 134 18508147

상세보기
26 Skjørringe T. Gjetting T. Jensen T.G. A modified protocol for efficient DNA encapsulation into pegylated immunoliposomes (PILs) J. Control. Release 139 2009 140 145 19545595

상세보기
27 Singer M. Deutschman C.S. Seymour C.W. Shankar-Hari M. Annane D. Bauer M. Bellomo R. Bernard G.R. Chiche J.D. Coopersmith C.M. Hotchkiss R.S. Levy M.M. Marshall J.C. Martin G.S. Opal S.M. Rubenfeld G.D. van der Poll T. Vincent J.L. Angus D.C. The third international consensus definitions for sepsis and septic shock (Sepsis-3) JAMA 315 2016 801 810 26903338

상세보기
28 H.H. Park, H.N. Kim, H. Kim, Y. Yoo, H. Shin, E.Y. Choi, J.-S. Bae, W. Lee, 6, 2020, p. eabc1564.
29 Rittirsch D. Huber-Lang M.S. Flierl M.A. Ward P.A. Immunodesign of experimental sepsis by cecal ligation and puncture Nat. Protoc. 4 2009 31 36 19131954

상세보기
30 Sun F. Xiao G. Qu Z. In vitro assay to assess efficacy of potential antiviral compounds against enterovirus D68 Bio-Protocol 7 2017

상세보기
31 Xu J. Zhou P. Wang W. Sun A. Guo F. RelB, together with RelA, sustains cell survival and confers proteasome inhibitor sensitivity of chronic lymphocytic leukemia cells from bone marrow J. Mol. Med. 92 2014 77 92 24042463
32 Guo C. Chi Z. Jiang D. Xu T. Yu W. Wang Z. Chen S. Zhang L. Liu Q. Guo X. Zhang X. Li W. Lu L. Wu Y. Song B.L. Wang D. Cholesterol homeostatic regulator SCAP-SREBP2 integrates NLRP3 inflammasome activation and cholesterol biosynthetic signaling in macrophages Immunity 49 2018 842 856.e7 e847 30366764

상세보기
33 Greenhalgh T. Koh G.C.H. Car J. Covid-19: a remote assessment in primary care BMJ 368 2020 m1182 32213507

상세보기
34 Tignanelli C.J. Ingraham N.E. Sparks M.A. Reilkoff R. Bezdicek T. Benson B. Schacker T. Chipman J.G. Puskarich M.A. Antihypertensive drugs and risk of COVID-19 Lancet Respir. Med. 8 2020 e30 e31 32222166

상세보기
35 Hoffmann M. Kleine-Weber H. Schroeder S. Krüger N. Herrler T. Erichsen S. Schiergens T.S. Herrler G. Wu N.-H. Nitsche A. Focus on causality in ESC/iPSC-based modeling of psychiatric disorders Cells 9 2020 366-280.e8

상세보기
36 Kao K.C. Chiu L.C. Hung C.Y. Chang C.H. Yang C.T. Huang C.C. Hu H.C. Coinfection and mortality in pneumonia-related acute respiratory distress syndrome patients with bronchoalveolar lavage: a prospective observational study Shock 47 2017 615 620 28410546

상세보기
37 Ye Q. Wang B. Mao J. The pathogenesis and treatment of the ‘Cytokine Storm’ in COVID-19 J. Infect. 80 2020 607 613 32283152

상세보기
38 Wang H. Ma S. The cytokine storm and factors determining the sequence and severity of organ dysfunction in multiple organ dysfunction syndrome Am. J. Emerg. Med. 26 2008 711 715 18606328
39 Hajj J. Blaine N. Salavaci J. Jacoby D. Healthcare 6 2018 (Basel)
40 Lin G.L. McGinley J.P. Drysdale S.B. Pollard A.J. Epidemiology and immune pathogenesis of viral sepsis Front. Immunol. 9 2018 2147 30319615
41 Zhang W. Zhao Y. Zhang F. Wang Q. Li T. Liu Z. Wang J. Qin Y. Zhang X. Yan X. Zeng X. Zhang S. The use of anti-inflammatory drugs in the treatment of people with severe coronavirus disease 2019 (COVID-19): the perspectives of clinical immunologists from China Clin. Immunol. 214 2020 108393

상세보기
42 Pooladanda V. Thatikonda S. Godugu C. The current understanding and potential therapeutic options to combat COVID-19 Life Sci. 254 2020 117765
43 Liu Q. Zhou Y.-h. Yang Z.-q. The cytokine storm of severe influenza and development of immunomodulatory therapy Cell. Mol. Immunol. 13 2016 3 10 26189369
44 Xiao H. Lu M. Lin T.Y. Chen Z. Chen G. Wang W.-C. Marin T. Shentu T.-p. Wen L. Gongol B. Sterol regulatory element binding protein 2 activation of NLRP3 inflammasome in endothelium mediates hemodynamic-induced atherosclerosis susceptibility Circulation 128 2013 632 642 23838163

상세보기
45 Zu S. Deng Y.-Q. Zhou C. Li J. Li L. Chen Q. Li X.-F. Zhao H. Gold S. He J. 25-Hydroxycholesterol is a potent SARS-CoV-2 inhibitor Cell Res. 30 2020 1043 1045 32811977
46 Zang R. Case J.B. Yutuc E. Ma X. Shen S. Castro M.F.G. Liu Z. Zeng Q. Zhao H. Son J. Cholesterol 25-hydroxylase suppresses SARS-CoV-2 replication by blocking membrane fusion Proc. Natl. Acad. Sci. USA 117 2020 32105 32113 33239446

상세보기

LOADING...

활용도 분석정보

상세보기

다운로드

내보내기

활용도 Top5 논문

해당 논문의 주제분야에서 활용도가 높은 상위 5개 콘텐츠를 보여줍니다.
더보기 버튼을 클릭하시면 더 많은 관련자료를 살펴볼 수 있습니다.

표제어: PCR

동의어: Packet Collision Rate

용어 설명 출처 목록 (6)

용어 설명: PCR은 세균 특이성이 있는 primer를 이용하여 적은 수의 세균이 있을지라도 쉽게 검출할 수 있는 유용한 방법이며, 이를 이용하여 구강 내 치면세균막이나 타액에서 직접 세균을 검출할 수 있게 되었다[8].

내보내기 구분	파일저장 인쇄 메일전송
구성항목	기본정보 상세정보 관리번호, 논문명, 저널/프로시딩명, 저자 , 발행년, 권, 호, 시작페이지, 끝페이지, 발행기관 관리번호, 논문명, 대등논문명, 저자 , 저널/프로시딩명, 발행기관, 발행년, 발행언어, 권, 호, 시작페이지, 끝페이지, ISBN, ISSN, 주제분야, 키워드, 초록(한글), 초록(영문), 저자(소속기관)
저장형식	Text(ASCII format) Excel format RefWorks Direct Export RIS format (for Reference Manager, ProCite, EndNote), Scholar's Aids, Mendeley
메일정보	받는사람 (필수) @ 보내는사람 (선택) @ 제목 내용 KISTI 검색결과 이메일 서비스
안내	총 건의 자료가 검색되었습니다. 다운받으실 자료의 인덱스를 입력하세요. (1-10,000) 검색결과의 순서대로 최대 10,000건 까지 다운로드가 가능합니다. 데이타가 많을 경우 속도가 느려질 수 있습니다.(최대 2~3분 소요) 다운로드 파일은 UTF-8 형태로 저장됩니다. 파일의 내용이 제대로 보이지 않을실 때는 웹브라우저 상단의 보기 -> 인코딩 -> 자동선택 여부를 확인하십시오. ~ Text(ASCII format) Excel format

연합인증