3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitor Atorvastatin mediated effects depend on the activation status of target cells in PLP-EAE.
The effect of Atorvastatin on transcriptional activity in murine experimental autoimmune encephalomyelitis (EAE) induced by PLP peptide 139-151 was analyzed by DNA microarray technique in lymph nodes and spinal cord at onset (10 days), height (20 days) and first remission (30 days) of disease. Fourteen genes were selectively influenced by Atorvastatin in EAE mice. They are mainly related to immune cell functions and regulation of cell-to-cell interaction. Interestingly, seven genes were also differentially regulated in CFA-injected control mice. But qualitative and quantitative differences to EAE mice argue for a dependency of statin effects on the activation status of target cells. Differential regulation of the newly detected candidate genes of statin effects COX-1 and HSP-105 and the previously known statin-responsive genes ICAM-1 and CD86 was confirmed by Western blot and immunohistochemistry. Flow cytometric analysis of lymph node cells revealed that the effect of Atorvastatin treatment in non-immunized healthy animals resembled the effect of immunization with PLP peptide regarding changes of T helper cells, activated B cells and macrophages. In EAE mice, these effects were partially reversed by Atorvastatin treatment. Monitoring of expression of the newly identified candidate genes and patterns of lymphocyte subpopulations might predict the responsiveness of multiple sclerosis patients to statin treatment.
Mix
Eilhard
E
Department of Neurology, University of Rostock, Gehlsheimer Str. 20, D-18147 Rostock, Germany.
Ibrahim
Saleh M
SM
Pahnke
Jens
J
Glass
Anne
A
Mazón-Peláez
Ignacio
I
Lemcke
Susanne
S
Koczan
Dirk
D
Gimsa
Ulrike
U
Bansemer
Sven
S
Scheel
Thomas
T
Karopka
Thomas
T
Böttcher
Tobias
T
Müller
Jana
J
Dazert
Eike
E
Antipova
Veronica
V
Hoffrogge
Raimund
R
Wree
Andreas
A
Zschiesche
Marlies
M
Strauss
Ulf
U
Kundt
Günther
G
Warzok
Rolf
R
Gierl
Lothar
L
Rolfs
Arndt
A
D000818:Animals; D000069059:Atorvastatin; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics / Q000276:immunology; D005434:Flow Cytometry; D015870:Gene Expression; D006538:Heptanoic Acids / Q000494:pharmacology*; D006903:Hydroxymethylglutaryl CoA Reductases / Q000378:metabolism*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000378:metabolism / Q000494:pharmacology*; D007962:Leukocytes / Q000276:immunology; D008198:Lymph Nodes / Q000276:immunology; D008297:Male; D051379:Mice; D009103:Multiple Sclerosis / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics / Q000276:immunology; D018991:Myelin Proteolipid Protein; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D010446:Peptide Fragments; D011758:Pyrroles / Q000494:pharmacology*; D013116:Spinal Cord / Q000276:immunology
D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D018991:Myelin Proteolipid Protein; D010446:Peptide Fragments; D011758:Pyrroles; C435023:myelin proteolipid protein (139-151); D000069059:Atorvastatin; D006903:Hydroxymethylglutaryl CoA Reductases