Linked Life Data

17661402

Source:http://linkedlifedata.com/resource/pubmed/id/17661402

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2007-11-5
pubmed:abstractText
In nonalcoholic fatty liver disease, the pathogenesis of progression from simple steatosis to steatohepatitis has not been fully clarified. Many factors, including oxidative stress and hepatic immune regulation, contribute to the inflammation in steatosis. Because regulatory T cells (Tregs) are important components of immune regulation, we have now investigated their role in the pathogenesis of nonalcoholic steatohepatitis. Wild-type C57BL/6 mice were fed a high-fat (HF) diet to induce steatosis, and the hepatic lymphocyte population was analyzed by flow cytometry. HF-induced steatosis was associated with the depletion of hepatic Tregs and led to up-regulation of the inflammatory tumor necrosis factor-alpha signaling pathway. When challenged by exogenous lipopolysaccharide, the HF-fed mice developed liver inflammation. In contrast, the adoptive transfer of Tregs decreased inflammation in HF-fed mice. In comparison with effector T cells, Tregs had a lower expression of Bcl-2 and, therefore, increased susceptibility to oxidative stress-induced apoptosis. The treatment of mice with the antioxidant Mn(III)tetrakis(4-benzoic acid)porphyrin chloride reduced Treg apoptosis, increased the number of hepatic Tregs, and decreased hepatic inflammation in HF-fed mice. CONCLUSION: Our results indicate that increased oxidative stress in a fatty liver causes the apoptosis of Tregs, reduces the number of hepatic Tregs, and leads to a lowered suppression of inflammatory responses. This scenario is likely one of the pathogenetic mechanisms that facilitate the transformation of simple steatosis into steatohepatitis when a fatty liver is exposed to second or third hits.
pubmed:grant
pubmed:commentsCorrections
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1527-3350
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
46
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1519-29
pubmed:dateRevised
2008-3-11
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
A high-fat diet and regulatory T cells influence susceptibility to endotoxin-induced liver injury.
pubmed:affiliation
Department of Gastroenterology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Institute of Digestive Disease, Shanghai, China.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural