Document Detail


Chronically inflamed livers up-regulate expression of inhibitory B7 family members.
MedLine Citation:
PMID:  19739236     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Hepatitis B virus, hepatitis C virus, autoimmune hepatitis, and nonalcoholic fatty liver disease can induce chronic liver disease. The Programmed Death-1 (PD-1) inhibitory pathway assists in T cell response regulation during acute and chronic inflammation and participates in the progression of inflammatory liver disease. To examine whether PD-1 and its ligands, B7-H1 and B7-DC, are modulated during chronic necroinflammatory liver disease, we investigated expression profiles in normal patients and patients with the aforementioned conditions. Relative to liver biopsies from normal individuals, those from patients with chronic necroinflammatory liver diseases (hepatitis B virus, hepatitis C virus, and autoimmune hepatitis) contain increased numbers of PD-1-expressing lymphocytes. Kupffer cells, liver sinusoidal endothelial cells, and leukocytes express PD-1 ligands. We also detect PD-1 ligands on hepatocytes within biopsies and on isolated cells. All forms of chronic necroinflammatory liver disease examined correlate with increased B7-H1 and B7-DC expression on Kupffer cells, liver sinusoidal epithelial cells, and leukocytes. The degree of necroinflammation correlates with expression levels of PD-1 family members. CONCLUSION: These results demonstrate that expression of PD-1/PD-1 ligands links more directly with the degree of inflammation than with the underlying etiology of liver damage. The PD-1 pathway may assist the liver in protecting itself from immune-mediated destruction.
Authors:
Rachel Kassel; Michael W Cruise; Julia C Iezzoni; Nicholas A Taylor; Timothy L Pruett; Young S Hahn
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  Hepatology (Baltimore, Md.)     Volume:  50     ISSN:  1527-3350     ISO Abbreviation:  Hepatology     Publication Date:  2009 Nov 
Date Detail:
Created Date:  2009-11-05     Completed Date:  2009-12-03     Revised Date:  2011-09-26    
Medline Journal Info:
Nlm Unique ID:  8302946     Medline TA:  Hepatology     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1625-37     Citation Subset:  IM    
Affiliation:
Carter Immunology Center, Department of Microbiology, University of Virginia, Charlottesville, VA 22908, USA.
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MeSH Terms
Descriptor/Qualifier:
Adult
Antigens, CD / metabolism*
Antigens, CD80 / metabolism*
Apoptosis Regulatory Proteins / metabolism
Biopsy
Case-Control Studies
Cells, Cultured
Fatty Liver / metabolism*,  pathology
Hepatitis B / metabolism*,  pathology
Hepatitis C / metabolism*,  pathology
Hepatitis, Autoimmune / metabolism*,  pathology
Hepatocytes / metabolism,  pathology
Humans
Leukocytes / metabolism,  pathology
Liver / metabolism*,  pathology
Lymphocytes / metabolism,  pathology
Middle Aged
Grant Support
ID/Acronym/Agency:
5-T32-AI007046/AI/NIAID NIH HHS; 5-T32-GM007267/GM/NIGMS NIH HHS; DK066754/DK/NIDDK NIH HHS; R01 DK066754-05/DK/NIDDK NIH HHS; T32 AI007046-27/AI/NIAID NIH HHS; T32 GM007267-31/GM/NIGMS NIH HHS; U19 AI066328-020001/AI/NIAID NIH HHS; U19 AI066328-040003/AI/NIAID NIH HHS; U19AI066328/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
0/Antigens, CD; 0/Antigens, CD80; 0/Apoptosis Regulatory Proteins; 0/B7-DC antigen; 0/CD274 protein, human; 146588-21-8/PDCD1 protein, human

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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