3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitor Atorvastatin mediated effects depend on the activation status of target cells in PLP-EAE

Eilhard Mix, Saleh M. Ibrahim, Jens Pahnke, Änne Glass, Ignacio Mazón-Peláez, Susanne Lemcke, Dirk Koczan, Ulrike Gimsa, Sven Bansemer, Thomas Scheel, Thomas Karopka, Tobias Böttcher, Jana Müller, Eike Dazert, Veronica Antipova, Raimund Hoffrogge, Andreas Wree, Marlies Zschiesche, Ulf Strauß, Günther KundtRolf Warzok, Lothar Gierl, Arndt Rolfs

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

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.

Original languageBritish English
Pages (from-to)251-265
Number of pages15
JournalJournal of Autoimmunity
Volume27
Issue number4
DOIs
StatePublished - Dec 2006

Keywords

  • Experimental autoimmune encephalomyelitis (EAE)
  • Immunohistochemistry
  • Leukocyte subpopulations
  • Lymph nodes
  • Oligonucleotide microarray
  • Spinal cord
  • Statin
  • Western blot

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