{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T05:30:40Z","timestamp":1790746240547,"version":"4.1.0"},"reference-count":43,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2019,2,12]],"date-time":"2019-02-12T00:00:00Z","timestamp":1549929600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"},{"start":{"date-parts":[[2019,2,12]],"date-time":"2019-02-12T00:00:00Z","timestamp":1549929600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2019,2,12]],"date-time":"2019-02-12T00:00:00Z","timestamp":1549929600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81571535"],"award-info":[{"award-number":["81571535"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81373143"],"award-info":[{"award-number":["81373143"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81571535"],"award-info":[{"award-number":["81571535"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81373143"],"award-info":[{"award-number":["81373143"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2019,3,22]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>NK cells are important in regulating hepatic fibrosis via their cytotoxic killing of hepatic stellate cells (HSCs). NK cells are activated by both cytokines such as IL-12 and IL-18, and innate immune stimuli such as ligation of TLRs. The secretion of IL-18 depends upon activation of the inflammasome, whereas TLRs are stimulated by microbial products. In the case of NK cells, IL-18 acts synergistically with stimulation of TLR3 to cause cell activation and cytotoxic function. In the present study, we activated NK cells to kill HSCs via IL-18 and TLR3 ligand stimulation, and dissected the signaling pathways or molecules critical for such activation or killing. We find that such activation depends on signaling via the p38\/PI3K\/AKT pathway, and that the activated NK cells mediate HSC death in a TRAIL-involved mechanism. As liver fibrosis is a major global health problem with no good solution, these results emphasize that the p38\/PI3K\/AKT pathway in NK cells may be a novel drug target to promote fibrosis regression.<\/jats:p>","DOI":"10.1002\/jlb.2a0118-031rr","type":"journal-article","created":{"date-parts":[[2019,2,12]],"date-time":"2019-02-12T18:43:51Z","timestamp":1549997031000},"page":"695-704","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":43,"title":["Activated NK cells kill hepatic stellate cells via p38\/PI3K signaling in a TRAIL-involved degranulation manner"],"prefix":"10.1093","volume":"105","author":[{"given":"Tianyang","family":"Li","sequence":"first","affiliation":[{"name":"Institute of Translational Medicine, Jilin University , Changchun, Jilin, China"},{"name":"Infectious Disease, The Second Affiliated Hospital of Guangzhou Medical University , Guangzhou, Guangdong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Yang","sequence":"additional","affiliation":[{"name":"Institute of Translational Medicine, Jilin University , Changchun, Jilin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongxiao","family":"Song","sequence":"additional","affiliation":[{"name":"Institute of Translational Medicine, Jilin University , Changchun, Jilin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haijun","family":"Li","sequence":"additional","affiliation":[{"name":"Institute of Translational Medicine, Jilin University , Changchun, Jilin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"An","family":"Cui","sequence":"additional","affiliation":[{"name":"Institute of Translational Medicine, Jilin University , Changchun, Jilin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanhou","family":"Liu","sequence":"additional","affiliation":[{"name":"Institute of Translational Medicine, Jilin University , Changchun, Jilin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lishan","family":"Su","sequence":"additional","affiliation":[{"name":"Institute of Translational Medicine, Jilin University , Changchun, Jilin, China"},{"name":"Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill , Chapel Hill, North Carolina, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian Nicholas","family":"Crispe","sequence":"additional","affiliation":[{"name":"Institute of Translational Medicine, Jilin University , Changchun, Jilin, China"},{"name":"Department of Pathology, University of Washington , Seattle, Washington, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhengkun","family":"Tu","sequence":"additional","affiliation":[{"name":"Institute of Translational Medicine, Jilin University , Changchun, Jilin, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2019,2,12]]},"reference":[{"key":"2023032406191631000_jlb10339-cit-0001","doi-asserted-by":"crossref","first-page":"1249","DOI":"10.1053\/j.gastro.2011.06.061","article-title":"Frequency and outcomes of liver transplantation for nonalcoholic steatohepatitis in the United States?","volume":"141","author":"Charlton","year":"2011","journal-title":"Gastroenterology"},{"key":"2023032406191631000_jlb10339-cit-0002","doi-asserted-by":"crossref","first-page":"812","DOI":"10.1053\/j.gastro.2016.11.020","article-title":"Incidence of hepatocellular carcinoma in all 50 United States, from 2000 through 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