Detailed Information

Cited 0 time in webofscience Cited 0 time in scopus
Metadata Downloads

Autophagy induced by AXL receptor tyrosine kinase alleviates acute liver injury via inhibition of NLRP3 inflammasome activation in mice

Authors
Han, JihyeBae, JoonbeomChoi, Chang-YongChoi, Sang-PilKang, Hyung-SikJo, Eun-KyeongPark, JongsunLee, Young SikMoon, Hyun-SeukPark, Chung-GyuLee, Myung-ShikChun, Taehoon
Issue Date
2016
Publisher
TAYLOR & FRANCIS INC
Keywords
autophagy; AXL receptor tyrosine kinase; hepatic inflammation; macrophage; NLRP3 inflammasome
Citation
AUTOPHAGY, v.12, no.12, pp.2326 - 2343
Indexed
SCIE
SCOPUS
Journal Title
AUTOPHAGY
Volume
12
Number
12
Start Page
2326
End Page
2343
URI
https://scholar.korea.ac.kr/handle/2021.sw.korea/90179
DOI
10.1080/15548627.2016.1235124
ISSN
1554-8627
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, ) 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.
Files in This Item
There are no files associated with this item.
Appears in
Collections
College of Life Sciences and Biotechnology > Division of Biotechnology > 1. Journal Articles
Graduate School > Department of Biotechnology > 1. Journal Articles

qrcode

Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.

Related Researcher

Researcher Lee, Young sik photo

Lee, Young sik
융합생명공학과
Read more

Altmetrics

Total Views & Downloads

BROWSE