TITLE

NKp46-mediated killing of human and mouse hepatic stellate cells attenuates liver fibrosis

AUTHOR(S)
Gur, Chamutal; Doron, Sarit; Kfir-Erenfeld, Shlomit; Horwitz, Elad; Abu-tair, Lina; Safadi, Rifaat; Mandelboim, Ofer
PUB. DATE
June 2012
SOURCE
Gut;Jun2012, Vol. 61 Issue 6, p885
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
Background Liver fibrosis, which involves activation of hepatic stellate cells (HSC), is a major health problem and is the end outcome of all chronic liver diseases. The liver is populated with lymphocytes, among which are natural killer (NK) cells, whose activity is controlled by inhibitory and activating receptors. NKp46, one of the major NK activating receptors expressed by NK cells, is also a specific NK marker that discriminates NK cells from all other lymphocyte subsets. It recognises viral haemagglutinins and unknown cellular ligands. Methods The anti-fibrotic activity of the NKp46 receptor was assessed in vivo and in vitro using NKp46-deficient mice (NCR1gfp/gfp), the carbon tetrachloride model and in vitro NK killing assays. Primary murine and human HSC were stained for the expression of the NKp46 ligand using fusion proteins composed of the extracellular portions of the murine and human NKp46 receptors fused to human IgG1. Results It was shown that murine HSC express a ligand for the murine orthologue of the NKp46 receptor, NCR1. NCR1 inhibited liver fibrosis in vivo; in vitro, murine HSC were killed in an NCR1-dependent manner. In humans it was shown that human HSC also express a ligand for the human NKp46 receptor and that the killing of human HSC is NKp46 dependent. Conclusions In addition to NKG2D, NKp46/NCR1 play an important role in inhibition of liver fibrosis. This suggests that fibrosis can be better controlled through the manipulation of NKp46 activity. INSET: Significance of this study.
ACCESSION #
76111440

 

Related Articles

  • A novel synthetic oleanolic acid derivative (CPU-II2) attenuates liver fibrosis in mice through regulating the function of hepatic stellate cells. Li-Mei Wu; Xing-Xin Wu; Yang Sun; Xiang-Wen Kong; Yi-Hua Zhang; Qiang Xu // Journal of Biomedical Science;Mar2008, Vol. 15 Issue 2, p251 

    Regulation on the function of the hepatic stellate cells (HSCs) is one of the proposed therapeutic approaches to liver fibrosis. In the present study, we examined the in vitro and in vivo effects of CPU-II2, a novel synthetic oleanolic acid (OLA) derivative with nitrate, on hepatic fibrosis....

  • Treatment with 4-Methylpyrazole Modulated Stellate Cells and Natural Killer Cells and Ameliorated Liver Fibrosis in Mice. Yi, Hyon-Seung; Eun, Hyuk Soo; Lee, Young-Sun; Jung, Ju Yeon; Park, Seol-Hee; Park, Keun-Gyu; Choi, Hueng-Sik; Suh, Jae Myoung; Jeong, Won-Il // PLoS ONE;May2015, Vol. 10 Issue 5, p1 

    Background & Aims: Accumulating evidence suggests that retinol and its metabolites are closely associated with liver fibrogenesis. Recently, we demonstrated that genetic ablation of alcohol dehydrogenase 3 (ADH3), a retinol metabolizing gene that is expressed in hepatic stellate cells (HSCs)...

  • Mesenchymal Stem Cells Pretreated with HGF and FGF4 Can Reduce Liver Fibrosis in Mice. Shams, Sulaiman; Mohsin, Sadia; Nasir, Ghazanfar Ali; Khan, Mohsin; Khan, Shaheen N. // Stem Cells International;1/20/2015, Vol. 2015, p1 

    Stem cells have opened a new avenue to treat liver fibrosis. We investigated in vitro and in vivo the effect of cytokine (HGF and FGF4) pretreated MSCs in reduction of CCl4 liver injury. Mouse MSCs were pretreated with cytokines to improve their ability to reduce CCl4 injury. In vitro we gave...

  • Knockdown of N-Acetylglucosaminyl Transferase V Ameliorates Hepatotoxin-Induced Liver Fibrosis in Mice. Liu, Junyu; Zhang, Zhengping; Tu, Xiaolong; Liu, Jialin; Zhang, Haiyan; Zhang, Jingcheng; Zang, Yuhui; Zhu, Jie; Chen, Jiangning; Dong, Lei; Zhang, Junfeng // Toxicological Sciences;Sep2013, Vol. 135 Issue 1, p144 

    Aberrant N-glycosylation caused by altered N-acetyl glucosaminyltransferase V (GnT-V) expression is known to regulate tumor invasion and metastasis by modulating multiple cytokine signaling pathways. However, the exact role of GnT-V in the development of liver fibrosis has not been clearly...

  • Mouse model of carbon tetrachloride induced liver fibrosis: Histopathological changes and expression of CD133 and epidermal growth factor. Fujii, Tsutomu; Fuchs, Bryan C.; Yamada, Suguru; Lauwers, Gregory Y.; Kulu, Yakup; Goodwin, Jonathan M.; Lanuti, Michael; Tanabe, Kenneth K. // BMC Gastroenterology;2010, Vol. 10, p79 

    Background: In the setting of chronic liver injury in humans, epidermal growth factor (EGF) and EGF receptor (EGFR) are up-regulated and have been proposed to have vital roles in both liver regeneration and development of hepatocellular carcinoma (HCC). Chronic liver injury also leads to hepatic...

  • R-Spondin2 Activates Hepatic Stellate Cells and Promotes Liver Fibrosis. Yin, Xinguang; Yi, Huixing; Wu, Wanxin; Shu, Jing; Wu, Xiaojun; Yu, Linghua // Digestive Diseases & Sciences;Oct2014, Vol. 59 Issue 10, p2452 

    Background: The development of liver fibrosis is the fundamental stage toward a number of mortal complications of liver diseases, including cirrhosis and hepatocellular carcinoma. Canonical Wnt pathway is crucial in diverse biological processes and mediates the progression and regression of...

  • Dietary olive oil prevents carbon tetrachloride-induced hepatic fibrosis in mice. Tanaka, Nobuyuki; Kono, Hiroshi; Ishii, Kenichi; Hosomura, Naohiro; Fujii, Hideki // Journal of Gastroenterology;2009, Vol. 44 Issue 9, p983 

    The specific purpose of this study was to investigate the effects of dietary olive oil on hepatic fibrosis induced by chronic administration of carbon tetrachloride (CCl4) in the mouse. In addition, the effects of oleic acid, a major component of olive oil, on activation of hepatic stellate...

  • Therapeutic effects of vitamin A on experimental cholestatic rats with hepatic fibrosis. Murakami, Ken-ichi; Kaji, Tatsuru; Shimono, Ryuichi; Hayashida, Yoshihiro; Matsufuji, Hiroshi; Tsuyama, Shinichiro; Maezono, Rie; Kosai, Ken-ichiro; Takamatsu, Hideo // Pediatric Surgery International;Aug2011, Vol. 27 Issue 8, p863 

    Purpose: The aim of this study is to investigate the role of hepatic stellate cells (HSCs) and the effect of vitamin A administration on liver damage induced by bile duct ligation (BDL) and administration of CCl(4).Methods: Two types of animal model were used; one was...

  • Systemic Delivery of scAAV8-Encoded MiR-29a Ameliorates Hepatic Fibrosis in Carbon Tetrachloride-Treated Mice. Knabel, Matthew K.; Ramachandran, Kalyani; Karhadkar, Sunil; Hwang, Hun-Way; Creamer, Tyler J.; Chivukula, Raghu R.; Sheikh, Farooq; Clark, K. Reed; Torbenson, Michael; Montgomery, Robert A.; Cameron, Andrew M.; Mendell, Joshua T.; Warren, Daniel S. // PLoS ONE;Apr2015, Vol. 10 Issue 4, p1 

    Fibrosis refers to the accumulation of excess extracellular matrix (ECM) components and represents a key feature of many chronic inflammatory diseases. Unfortunately, no currently available treatments specifically target this important pathogenic mechanism. MicroRNAs (miRNAs) are short,...

Share

Read the Article

Courtesy of THE LIBRARY OF VIRGINIA

Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics