Document Detail


Activation of liver X receptors and retinoid X receptors prevents bacterial-induced macrophage apoptosis.
MedLine Citation:
PMID:  15601766     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Microbe-macrophage interactions play a central role in the pathogenesis of many infections. The ability of some bacterial pathogens to induce macrophage apoptosis has been suggested to contribute to their ability to elude innate immune responses and successfully colonize the host. Here, we provide evidence that activation of liver X receptors (LXRs) and retinoid X receptors (RXRs) inhibits apoptotic responses of macrophages to macrophage colony-stimulating factor (M-CSF) withdrawal and several inducers of apoptosis. In addition, combined activation of LXR and RXR protected macrophages from apoptosis caused by infection with Bacillus anthracis, Escherichia coli, and Salmonella typhimurium. Expression-profiling studies demonstrated that LXR and RXR agonists induced the expression of antiapoptotic regulators, including AIM/CT2, Bcl-X(L), and Birc1a. Conversely, LXR and RXR agonists inhibited expression of proapoptotic regulators and effectors, including caspases 1, 4/11, 7, and 12; Fas ligand; and Dnase1l3. The combination of LXR and RXR agonists was more effective than either agonist alone at inhibiting apoptosis in response to various inducers of apoptosis, and it acted synergistically to induce expression of AIM/CT2. Inhibition of AIM/CT2 expression in response to LXR/RXR agonists partially reversed their antiapoptotic effects. These findings reveal unexpected roles of LXRs and RXRs in the control of macrophage survival and raise the possibility that LXR/RXR agonists may be exploited to enhance innate immunity to bacterial pathogens that induce apoptotic programs as a strategy for evading host responses.
Authors:
Annabel F Valledor; Li-Chung Hsu; Sumito Ogawa; Dominique Sawka-Verhelle; Michael Karin; Christopher K Glass
Related Documents :
9336406 - Fas/fas ligand expression and induction of apoptosis in chondrocytes.
19852076 - Effects of the fas/fas-l pathway on fluoride-induced apoptosis in sh-sy5y cells.
12522536 - Shedding of fas ectodomain that affects apoptosis of hepatocytes occurring in regenerat...
9521326 - Fas-mediated apoptosis and activation-induced t-cell proliferation are defective in mic...
24089506 - Suppression of inflammation with conditional deletion of the prostaglandin e2 ep2 recep...
17575126 - A novel role for p73 in the regulation of akt-foxo1a-bim signaling and apoptosis induce...
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.     Date:  2004-12-15
Journal Detail:
Title:  Proceedings of the National Academy of Sciences of the United States of America     Volume:  101     ISSN:  0027-8424     ISO Abbreviation:  Proc. Natl. Acad. Sci. U.S.A.     Publication Date:  2004 Dec 
Date Detail:
Created Date:  2004-12-22     Completed Date:  2005-02-04     Revised Date:  2013-04-18    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  United States    
Other Details:
Languages:  eng     Pagination:  17813-8     Citation Subset:  IM    
Affiliation:
Department of Cellular and Molecular Medicine, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Animals
Apoptosis* / drug effects
Apoptosis Regulatory Proteins
Cells, Cultured
DNA-Binding Proteins
Macrophages / cytology*,  drug effects,  metabolism*,  microbiology
Mice
Mice, Knockout
Orphan Nuclear Receptors
Receptors, Cytoplasmic and Nuclear / deficiency,  genetics,  metabolism*
Receptors, Immunologic / metabolism
Retinoid X Receptors / metabolism*
Grant Support
ID/Acronym/Agency:
AI061712/AI/NIAID NIH HHS; DK063491/DK/NIDDK NIH HHS; ES10337/ES/NIEHS NIH HHS; HL56989/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Apoptosis Regulatory Proteins; 0/Cd5l protein, mouse; 0/DNA-Binding Proteins; 0/Orphan Nuclear Receptors; 0/Receptors, Cytoplasmic and Nuclear; 0/Receptors, Immunologic; 0/Retinoid X Receptors; 0/liver X receptor
Comments/Corrections

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


Previous Document:  Ecosystem consequences of bird declines.
Next Document:  Who gets acknowledged: measuring scientific contributions through automatic acknowledgment indexing.