최제민 (한양대학교 생명과학과) | 한빛사논문 > 한빛사

한빛사논문

조회739

한양대학교 생명과학과

CV File 1 MB

Biomaterials, Available online 4 May 2021, 120845 | https://doi.org/10.1016/j.biomaterials.2021.120845 Macrophage-preferable delivery of the leucine-rich repeat domain of NLRX1 ameliorates lethal sepsis by regulating NF-κB and inflammasome signaling activation

Ja-Hyun Koo^a,b, Sang-Hun Kim^c, Soung-Hoo Jeon^a,b, Min-Jong Kang^c, Je-Min Choi^a,b,d,*

^aDepartment of Life Science, College of Natural Sciences, Hanyang University, Seoul 04763, Republic of Korea
^bResearch Institute for Natural Sciences, Hanyang University, Seoul 04763, Republic of Korea
^cSection of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06520, USA
^dResearch Institute for Convergence of Basic Sciences, Hanyang University, Seoul 04763, Republic of Korea

^*Corresponding author.

Abstract

Sepsis is an acute systemic inflammatory disease triggered by bacterial infection leading organ dysfunctions that macrophages are responsible for major triggering of systemic inflammation. Treatment options are limited to antibiotics and drugs to manage the symptoms of sepsis, but there are currently no molecular-targeted therapies. Here, we identified a novel macrophage-preferable delivery peptide, C10, which we conjugated to truncated domains of NLRX1 (leucine-rich repeat region (LRR), and nucleotide binding domain (NBD)) to obtain C10-LRR and C10-NBD. Leucine rich amino acid of C10 enables macrophage preferable moieties that efficiently deliver a cargo protein into macrophages in vitro and in vivo. C10-LRR but not C10-NBD significantly improved survival in an LPS-mediated lethal endotoxemia sepsis model. C10-LRR efficiently inhibited IL-6 production in peritoneal macrophages via prevention of IκB degradation and p65 phosphorylation. In addition, C10-LRR negatively regulated IL-1β production by preventing caspase-1 activation with a sustained mitochondrial MAVS level. Finally, co-treatment with anti-TNFα antibody and C10-LRR had a synergistic effect in an LPS-induced sepsis model. Collectively, these findings indicate that C10-LRR could be an effective therapeutic agent to treat systemic inflammation in sepsis by regulating both NF-κB and inflammasome signaling activation.

Keywords : Sepsis, NLRX1, Cell penetrating peptide, Macrophage, NF-κB, Inflammasome

논문정보

형식Research article
게재일2021년 05월 (BRIC 등록일 2021-05-11)
연구진국내(교신)+국외 연구진
분야 생명과학 > 면역학

댓글 작성 로그인

CV 열람하기

연락처 보기