한빛사논문
- 조회1,693
Abstract
Jihye Hana,†, Joonbeom Baea,†, Chang-Yong Choia, Sang-Pil Choia, Hyung-Sik Kangb, Eun-Kyeong Joc, Jongsun Parkd, Young Sik Leea, Hyun-Seuk Moona, Chung-Gyu Parke, Myung-Shik Leef and Taehoon Chuna,*
aDepartment of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul, Korea; bSchool of Biological Sciences and Technology, Biotechnology Research Institute, Chonnam National University, Kwangju, Korea; cInfection Signaling Network Research Center, Department of Microbiology, College of Medicine, Chungnam National University, Daejeon, Korea; dDepartment of Pharmacology, Metabolic Diseases and Cell Signaling Laboratory, Research Institute for Medical Sciences, College of Medicine, Chungnam National University, Daejeon, Korea; eDepartment of Microbiology and Immunology, Seoul National University College of Medicine, Seoul, Korea; fSeverance Biomedical Science Institute, Department of Internal Medicine, College of Medicine, Yonsei University, Seoul, Korea
†These authors contributed equally to this work.
*Correspondence : Taehoon Chun
Abstract
Severe hepatic inflammation is a common cause of acute or chronic liver disease. Macrophages are one of the key mediators which regulate the progress of hepatic inflammation. Increasing evidence shows that the TAM (TYRO3, AXL and MERTK) family of RTKs (receptor tyrosine kinases), which is expressed in macrophages, alleviates inflammatory responses through a negative feedback loop. However, the functional contribution of each TAM family member to the progression of hepatic inflammation remains elusive. In this study, we explore the role of individual TAM family proteins during autophagy induction and evaluate their contribution to hepatic inflammation. Among the TAM family of RTKs, AXL (AXL receptor tyrosine kinase) only induces autophagy in macrophages after interaction with its ligand, GAS6 (growth arrest specific 6). Based on our results, autophosphorylation of 2 tyrosine residues (Tyr815 and Tyr860) in the cytoplasmic domain of AXL in mice is required for autophagy induction and AXL-mediated autophagy induction is dependent on MAPK (mitogen-activated protein kinase)14 activity. Furthermore, induction of AXL-mediated autophagy prevents CASP1 (caspase 1)-dependent IL1B (interleukin 1, beta) and IL18 (interleukin 18) maturation by inhibiting NLRP3 (NLR family, pyrin domain containing 3) inflammasome activation. In agreement with these observations, axl-/- mice show more severe symptoms than do wild-type (Axl+/+) mice following acute hepatic injury induced by administration of lipopolysaccharide (LPS) or carbon tetrachloride (CCl4). Hence, GAS6-AXL signaling-mediated autophagy induction in murine macrophages ameliorates hepatic inflammatory responses by inhibiting NLRP3 inflammasome activation.
Keywords: autophagy, AXL receptor tyrosine kinase, hepatic inflammation, macrophage, NLRP3 inflammasome
논문정보
- Research article
- 2016년 10월 (BRIC 등록일 2016-11-03)
- 국내 연구진
- 생명과학 > 면역학
댓글 작성 로그인
팝업 닫기관련 링크
연구자 키워드
연구자 ID
관련분야 연구자보기
소속기관 논문보기
관련분야 논문보기
해당논문 저자보기
