PMID- 17175031
OWN - NLM
STAT- MEDLINE
DCOM- 20070405
LR  - 20220409
IS  - 0165-5728 (Print)
IS  - 0165-5728 (Linking)
VI  - 183
IP  - 1-2
DP  - 2007 Feb
TI  - Liver X receptor and retinoid X receptor agonists inhibit inflammatory responses 
      of microglia and astrocytes.
PG  - 50-9
AB  - Liver X receptors (LXRs) are nuclear receptors previously identified to be 
      important in lipid metabolism. Recent reports suggest that LXR agonists also 
      exhibit anti-inflammatory properties in mouse models of atherosclerosis and 
      contact dermatitis. In the present study, we investigated the effects of LXR 
      agonists on mouse microglia and astrocytes. When chronically activated, these 
      resident-CNS glia have been implicated in the pathology of neuroinflammatory 
      disorders including multiple sclerosis (MS). Our studies demonstrated for the 
      first time that LXR agonists inhibited the production of nitric oxide, the 
      pro-inflammatory cytokines IL-1beta and IL-6 and the chemokine MCP-1 from 
      LPS-stimulated microglia and astrocytes. Furthermore, LXR agonists inhibited 
      LPS-induction of nuclear factor-kappa B (NF-kappaB) DNA-binding activity. These 
      agonists also blocked LPS-induction of IkappaB-alpha protein degradation in 
      microglia, suggesting a mechanism by which these agonists modulate NF-kappaB 
      DNA-binding activity. These studies suggest that LXR agonists suppress the 
      production of pro-inflammatory molecules by CNS glia, at least in part, by 
      modulating NF-kappaB-signaling pathways. Retinoid X receptors (RXRs) physically 
      interact with LXR receptors, and the resulting obligate heterodimer regulates the 
      expression of LXR-responsive genes. Interestingly, a combination of LXR and RXR 
      agonists additively suppressed the production of NO by microglia and astrocytes. 
      Collectively, these studies suggest that LXR agonists may be effective in the 
      treatment of neuroinflammatory diseases including MS.
FAU - Zhang-Gandhi, Cindy X
AU  - Zhang-Gandhi CX
AD  - Department of Neurobiology and Developmental Sciences, University of Arkansas for 
      Medical Sciences, Little Rock, Arkansas 72205, USA.
FAU - Drew, Paul D
AU  - Drew PD
LA  - eng
GR  - NS047546/NS/NINDS NIH HHS/United States
GR  - P30 NS047546-03/NS/NINDS NIH HHS/United States
GR  - R01 NS042860/NS/NINDS NIH HHS/United States
GR  - P30 NS047546/NS/NINDS NIH HHS/United States
GR  - NS42860/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20061218
PL  - Netherlands
TA  - J Neuroimmunol
JT  - Journal of neuroimmunology
JID - 8109498
RN  - 0 (Cytokines)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Hydrocarbons, Fluorinated)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Liver X Receptors)
RN  - 0 (Orphan Nuclear Receptors)
RN  - 0 (Receptors, Cytoplasmic and Nuclear)
RN  - 0 (Retinoid X Receptors)
RN  - 0 (Sulfonamides)
RN  - 0 (T0901317)
RN  - 169D1260KM (Nitroprusside)
RN  - 31C4KY9ESH (Nitric Oxide)
SB  - IM
MH  - Analysis of Variance
MH  - Animals
MH  - Animals, Newborn
MH  - Astrocytes/*drug effects
MH  - Cell Survival/drug effects
MH  - Cells, Cultured
MH  - Cerebral Cortex/cytology
MH  - Cytokines/*metabolism
MH  - DNA-Binding Proteins/*agonists
MH  - Dose-Response Relationship, Drug
MH  - Drug Interactions
MH  - Gene Expression Regulation/drug effects
MH  - Hydrocarbons, Fluorinated
MH  - Lipopolysaccharides/pharmacology
MH  - Liver X Receptors
MH  - Mice
MH  - Microglia/*drug effects
MH  - Nitric Oxide/*metabolism
MH  - Nitroprusside/metabolism
MH  - Orphan Nuclear Receptors
MH  - Receptors, Cytoplasmic and Nuclear/*agonists
MH  - Retinoid X Receptors/*agonists
MH  - Sulfonamides/pharmacology
PMC - PMC2080645
MID - NIHMS18418
EDAT- 2006/12/19 09:00
MHDA- 2007/04/06 09:00
PMCR- 2008/02/01
CRDT- 2006/12/19 09:00
PHST- 2006/09/20 00:00 [received]
PHST- 2006/11/10 00:00 [revised]
PHST- 2006/11/13 00:00 [accepted]
PHST- 2006/12/19 09:00 [pubmed]
PHST- 2007/04/06 09:00 [medline]
PHST- 2006/12/19 09:00 [entrez]
PHST- 2008/02/01 00:00 [pmc-release]
AID - S0165-5728(06)00444-9 [pii]
AID - 10.1016/j.jneuroim.2006.11.007 [doi]
PST - ppublish
SO  - J Neuroimmunol. 2007 Feb;183(1-2):50-9. doi: 10.1016/j.jneuroim.2006.11.007. Epub 
      2006 Dec 18.