PMID- 15601766
OWN - NLM
STAT- MEDLINE
DCOM- 20050204
LR  - 20201209
IS  - 0027-8424 (Print)
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Linking)
VI  - 101
IP  - 51
DP  - 2004 Dec 21
TI  - Activation of liver X receptors and retinoid X receptors prevents 
      bacterial-induced macrophage apoptosis.
PG  - 17813-8
AB  - 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.
FAU - Valledor, Annabel F
AU  - Valledor AF
AD  - Department of Cellular and Molecular Medicine, University of California at San 
      Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA.
FAU - Hsu, Li-Chung
AU  - Hsu LC
FAU - Ogawa, Sumito
AU  - Ogawa S
FAU - Sawka-Verhelle, Dominique
AU  - Sawka-Verhelle D
FAU - Karin, Michael
AU  - Karin M
FAU - Glass, Christopher K
AU  - Glass CK
LA  - eng
GR  - AI061712/AI/NIAID NIH HHS/United States
GR  - P42 ES010337/ES/NIEHS NIH HHS/United States
GR  - P30 DK063491/DK/NIDDK NIH HHS/United States
GR  - HL56989/HL/NHLBI NIH HHS/United States
GR  - P50 HL056989/HL/NHLBI NIH HHS/United States
GR  - R01 AI061712/AI/NIAID NIH HHS/United States
GR  - DK063491/DK/NIDDK NIH HHS/United States
GR  - ES10337/ES/NIEHS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20041215
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (Apoptosis Regulatory Proteins)
RN  - 0 (Cd5l protein, mouse)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Liver X Receptors)
RN  - 0 (Orphan Nuclear Receptors)
RN  - 0 (Receptors, Cytoplasmic and Nuclear)
RN  - 0 (Receptors, Immunologic)
RN  - 0 (Receptors, Scavenger)
RN  - 0 (Retinoid X Receptors)
SB  - IM
MH  - Animals
MH  - *Apoptosis/drug effects
MH  - Apoptosis Regulatory Proteins
MH  - Cells, Cultured
MH  - DNA-Binding Proteins
MH  - Liver X Receptors
MH  - Macrophages/*cytology/drug effects/*metabolism/microbiology
MH  - Mice
MH  - Mice, Knockout
MH  - Orphan Nuclear Receptors
MH  - Receptors, Cytoplasmic and Nuclear/deficiency/genetics/*metabolism
MH  - Receptors, Immunologic/metabolism
MH  - Receptors, Scavenger
MH  - Retinoid X Receptors/*metabolism
PMC - PMC539759
EDAT- 2004/12/17 09:00
MHDA- 2005/02/05 09:00
PMCR- 2005/06/21
CRDT- 2004/12/17 09:00
PHST- 2004/12/17 09:00 [pubmed]
PHST- 2005/02/05 09:00 [medline]
PHST- 2004/12/17 09:00 [entrez]
PHST- 2005/06/21 00:00 [pmc-release]
AID - 0407749101 [pii]
AID - 010117813 [pii]
AID - 10.1073/pnas.0407749101 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 2004 Dec 21;101(51):17813-8. doi: 
      10.1073/pnas.0407749101. Epub 2004 Dec 15.