PMID- 16764943
OWN - NLM
STAT- MEDLINE
DCOM- 20060929
LR  - 20161122
IS  - 0165-5728 (Print)
IS  - 0165-5728 (Linking)
VI  - 176
IP  - 1-2
DP  - 2006 Jul
TI  - Peroxisome proliferator-activated receptor-alpha and retinoid X receptor agonists 
      inhibit inflammatory responses of astrocytes.
PG  - 95-105
AB  - The peroxisome proliferator-activated receptor-alpha (PPAR-alpha) plays a key 
      role in lipid metabolism and inflammation. Recently, we demonstrated that 
      administration of the PPAR-alpha agonists gemfibrozil and fenofibrate, inhibit 
      the clinical signs of experimental autoimmune encephalomyelitis (EAE), an animal 
      model of multiple sclerosis (MS). In the present study, we investigated the 
      effects of PPAR-alpha agonists on primary mouse astrocytes, a cell type 
      implicated in the pathology of MS and EAE. Our studies demonstrated that the 
      PPAR-alpha agonists fenofibrate, and WY 14643 inhibited NO production by 
      LPS-stimulated astrocytes in a dose-dependent manner. Additionally, PPAR-alpha 
      agonists inhibited the secretion of the pro-inflammatory cytokines TNF-alpha, 
      IL-1beta, and IL-6 by LPS-stimulated astrocytes. Fenofibrate inhibited NF-kappaB 
      DNA binding activity, suggesting a mechanism by which PPAR-alpha agonists may 
      regulate the expression of genes encoding these pro-inflammatory molecules. 
      Retinoid X receptors (RXRs) physically interact with PPAR-alpha receptors, and 
      the resulting heterodimers regulate the expression of PPAR-responsive genes. 
      Interestingly, a combination of 9-cis RA and the PPAR-alpha agonists fenofibrate 
      or gemfibrozil cooperatively inhibited NO, TNF-alpha, IL-1beta, IL-6, and MCP-1 
      production by these cells. Collectively, these results raise the possibility that 
      PPAR-alpha and RXR agonists might be effective in the treatment of MS, where 
      activated astrocytes are believed to contribute to disease pathology.
FAU - Xu, Jihong
AU  - Xu J
AD  - Department of Neurobiology and Developmental Sciences, University of Arkansas for 
      Medical Sciences, Little Rock, AR 72205, USA.
FAU - Chavis, Janet A
AU  - Chavis JA
FAU - Racke, Michael K
AU  - Racke MK
FAU - Drew, Paul D
AU  - Drew PD
LA  - eng
GR  - P30 NS047546/NS/NINDS NIH HHS/United States
GR  - P30 NS047546-02/NS/NINDS NIH HHS/United States
GR  - NS42860/NS/NINDS NIH HHS/United States
GR  - NS 047546/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 - 20060609
PL  - Netherlands
TA  - J Neuroimmunol
JT  - Journal of neuroimmunology
JID - 8109498
RN  - 0 (Chemokines)
RN  - 0 (Cytokines)
RN  - 0 (NF-kappa B)
RN  - 0 (PPAR alpha)
RN  - 0 (Retinoid X Receptors)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - 9007-49-2 (DNA)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type II)
SB  - IM
MH  - Animals
MH  - Astrocytes/*drug effects/physiology
MH  - Chemokines/biosynthesis
MH  - Cytokines/biosynthesis
MH  - DNA/metabolism
MH  - Inflammation/*prevention & control
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Multiple Sclerosis/drug therapy
MH  - NF-kappa B/metabolism
MH  - Nitric Oxide/biosynthesis
MH  - Nitric Oxide Synthase Type II/biosynthesis
MH  - PPAR alpha/*agonists
MH  - Retinoid X Receptors/*agonists
EDAT- 2006/06/13 09:00
MHDA- 2006/09/30 09:00
CRDT- 2006/06/13 09:00
PHST- 2006/01/03 00:00 [received]
PHST- 2006/03/24 00:00 [revised]
PHST- 2006/04/14 00:00 [accepted]
PHST- 2006/06/13 09:00 [pubmed]
PHST- 2006/09/30 09:00 [medline]
PHST- 2006/06/13 09:00 [entrez]
AID - S0165-5728(06)00151-2 [pii]
AID - 10.1016/j.jneuroim.2006.04.019 [doi]
PST - ppublish
SO  - J Neuroimmunol. 2006 Jul;176(1-2):95-105. doi: 10.1016/j.jneuroim.2006.04.019. 
      Epub 2006 Jun 9.