Document Detail


Internalization of modified lipids by CD36 and SR-A leads to hepatic inflammation and lysosomal cholesterol storage in Kupffer cells.
MedLine Citation:
PMID:  22470565     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND & AIMS: Non-alcoholic steatohepatitis (NASH) is characterized by steatosis and inflammation, which can further progress into fibrosis and cirrhosis. Recently, we demonstrated that combined deletion of the two main scavenger receptors, CD36 and macrophage scavenger receptor 1 (MSR1), which are important for modified cholesterol-rich lipoprotein uptake, reduced NASH. The individual contributions of these receptors to NASH and the intracellular mechanisms by which they contribute to inflammation have not been established. We hypothesize that CD36 and MSR1 contribute independently to the onset of inflammation in NASH, by affecting intracellular cholesterol distribution inside Kupffer cells (KCs).
METHODS & RESULTS: Ldlr(-/-) mice were transplanted with wild-type (Wt), Cd36(-/-) or Msr1(-/-) bone marrow and fed a Western diet for 3 months. Cd36(-/-)- and Msr1(-/-)- transplanted (tp) mice showed a similar reduction in hepatic inflammation compared to Wt-tp mice. While the total amount of cholesterol inside KCs was similar in all groups, KCs of Cd36(-/-)- and Msr1(-/-)-tp mice showed increased cytoplasmic cholesterol accumulation, while Wt-tp mice showed increased lysosomal cholesterol accumulation.
CONCLUSION: CD36 and MSR1 contribute similarly and independently to the progression of inflammation in NASH. One possible explanation for the inflammatory response related to expression of these receptors could be abnormal cholesterol trafficking in KCs. These data provide a new basis for prevention and treatment of NASH.
Authors:
Veerle Bieghs; Fons Verheyen; Patrick J van Gorp; Tim Hendrikx; Kristiaan Wouters; Dieter Lütjohann; Marion J J Gijbels; Maria Febbraio; Christoph J Binder; Marten H Hofker; Ronit Shiri-Sverdlov
Related Documents :
7150645 - Influence of a low-selenium diet on erythrocyte glutathione peroxidase and alkane produ...
430245 - Glutathione peroxidase acitvity in intestinal and liver tissues of rats fed various lev...
1120735 - Experimentally induced vitamin e-selenium deficiency in the growing dog.
24476935 - Independent associations of income and education with nutrient intakes in brazilian adu...
195575 - Characterization of serum lipoproteins of the shark centrophorus squamous.
7995175 - Equine model of inducing ulceration in alimentary squamous epithelial mucosa.
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-03-28
Journal Detail:
Title:  PloS one     Volume:  7     ISSN:  1932-6203     ISO Abbreviation:  PLoS ONE     Publication Date:  2012  
Date Detail:
Created Date:  2012-04-03     Completed Date:  2012-08-03     Revised Date:  2014-05-27    
Medline Journal Info:
Nlm Unique ID:  101285081     Medline TA:  PLoS One     Country:  United States    
Other Details:
Languages:  eng     Pagination:  e34378     Citation Subset:  IM    
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Animals
Antigens, CD36 / deficiency,  genetics,  metabolism*
Bone Marrow Transplantation
Cholesterol / metabolism*
Fatty Liver / metabolism,  pathology
Female
Inflammation / pathology
Kupffer Cells / metabolism*,  pathology*
Lipid Metabolism*
Lipids / chemistry
Liver / metabolism,  pathology
Lysosomes / metabolism*
Mice
Mice, Knockout
Receptors, LDL / deficiency,  genetics,  metabolism
Scavenger Receptors, Class A / deficiency,  genetics,  metabolism*
Grant Support
ID/Acronym/Agency:
F 3015-B19//Austrian Science Fund FWF
Chemical
Reg. No./Substance:
0/Antigens, CD36; 0/Lipids; 0/Msr1 protein, mouse; 0/Receptors, LDL; 0/Scavenger Receptors, Class A; 97C5T2UQ7J/Cholesterol
Comments/Corrections

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


Previous Document:  The tandem CARDs of NOD2: intramolecular interactions and recognition of RIP2.
Next Document:  The early postnatal nonhuman primate neocortex contains self-renewing multipotent neural progenitor ...