Skip to content
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Menu
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Menu
Home
About Us
Resources
Profiles Metrics
Authors Directory
Institutions Directory
Top Authors
Top Institutions
Top Sponsors
AI Digest
Contact Us
Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
Inhibition of natural killer cells protects the liver against acute injury in the absence of glycine N-methyltransferase
Hepatology, Volume 56, No. 2, Year 2012
Notification
URL copied to clipboard!
Description
Glycine N-methyltransferase (GNMT) catabolizes S-adenosylmethionine (SAMe), the main methyl donor of the body. Patients with cirrhosis show attenuated GNMT expression, which is absent in hepatocellular carcinoma (HCC) samples. GNMT-/- mice develop spontaneous steatosis that progresses to steatohepatitis, cirrhosis, and HCC. The liver is highly enriched with innate immune cells and plays a key role in the body's host defense and in the regulation of inflammation. Chronic inflammation is the major hallmark of nonalcoholic steatohepatitis (NASH) progression. The aim of our study was to uncover the molecular mechanisms leading to liver chronic inflammation in the absence of GNMT, focusing on the implication of natural killer (NK)/natural killer T (NKT) cells. We found increased expression of T helper (Th)1- over Th2-related cytokines, tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL)-R2/DR5, and several ligands of NK cells in GNMT-/- livers. Interestingly, NK cells from GNMT-/- mice were spontaneously activated, expressed more TRAIL, and had strong cytotoxic activity, suggesting their contribution to the proinflammatory environment in the liver. Accordingly, NK cells mediated hypersensitivity to concanavalin A (ConA)-mediated hepatitis in GNMT-/- mice. Moreover, GNMT-/- mice were hypersensitive to endotoxin-mediated liver injury. NK cell depletion and adoptive transfer of TRAIL-/- liver-NK cells protected the liver against lipopolysaccharide (LPS) liver damage. Conclusion: Our data allow us to conclude that TRAIL-producing NK cells actively contribute to promote a proinflammatory environment at early stages of fatty liver disease, suggesting that this cell compartment may contribute to the progression of NASH. © 2012 American Association for the Study of Liver Diseases.
Authors & Co-Authors
Gomez-Santos, Laura
Spain, Madrid
Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas
Luka, Zigmund
United States, Nashville
Vanderbilt University
Wagner, Conrad
United States, Nashville
Vanderbilt University
Tunisia, Nashville
Medical Affairs Medical Center
Fernandez-Alvarez, Sara
Spain, Madrid
Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas
Lu, Shelly C.
United States, Los Angeles
Keck School of Medicine of Usc
Mato, José María
Spain, Madrid
Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas
Martinez-Chantar, Maria L.
Spain, Madrid
Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas
Beraza, Naiara
Spain, Madrid
Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas
Statistics
Citations: 8
Authors: 8
Affiliations: 4
Identifiers
Doi:
10.1002/hep.25694
ISSN:
02709139
Research Areas
Cancer
Infectious Diseases
Violence And Injury