Skip to main content
Journal cover image

Simvastatin inhibits secretion of Th17-polarizing cytokines and antigen presentation by DCs in patients with relapsing remitting multiple sclerosis.

Publication ,  Journal Article
Zhang, X; Tao, Y; Wang, J; Garcia-Mata, R; Markovic-Plese, S
Published in: Eur J Immunol
January 2013

Statins, widely used cholesterol-lowering agents, have also been demonstrated to have antiinflammatory effects. Here, we characterize the capacity of simvastatin to target DCs and modulate T-cell priming and Th17-cell differentiation, in a cohort of patients with relapsing remitting multiple sclerosis (RRMS). We report that simvastatin inhibits IL-1β, IL-23, TGF-β, IL-21, IL-12p70, and induces IL-27 secretion from DCs in RRMS patients, providing an inhibitory cytokine milieu for Th17 and Th1-cell differentiation. The effect on DCs is mediated via induction of SOCS1, SOCS3, and SOCS7 gene expression, which are associated with the inhibition of STAT1, STAT3, and ERK1/2 phosphorylation. A geranylgeranyl transferase inhibitor replicated simvastatin's effects on DC cytokine secretion, implicating that simvastatin-induced depletion of isoprenoids mediates this effect. Simvastatin inhibited antigen presentation by DCs via suppression of the MHC class I expression, costimulatory molecules CD80 and CD40, and by inducing a dramatic loss of dendritic processes. The changes in DC morphology were also mediated via inhibition of geranylgeranylation. The therapeutic use of geranylgeranylation inhibitors may provide selective inhibition of key pathogenic cytokines that drive the autoimmune response in MS; their use represents a promising therapeutic approach that requires further clinical testing.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

Eur J Immunol

DOI

EISSN

1521-4141

Publication Date

January 2013

Volume

43

Issue

1

Start / End Page

281 / 289

Location

Germany

Related Subject Headings

  • Young Adult
  • Th17 Cells
  • Th1-Th2 Balance
  • Th1 Cells
  • Simvastatin
  • Multiple Sclerosis, Relapsing-Remitting
  • Monocytes
  • Middle Aged
  • Male
  • Lymphocyte Activation
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Zhang, X., Tao, Y., Wang, J., Garcia-Mata, R., & Markovic-Plese, S. (2013). Simvastatin inhibits secretion of Th17-polarizing cytokines and antigen presentation by DCs in patients with relapsing remitting multiple sclerosis. Eur J Immunol, 43(1), 281–289. https://doi.org/10.1002/eji.201242566
Zhang, Xin, Yazhong Tao, Jinzhao Wang, Rafael Garcia-Mata, and Silva Markovic-Plese. “Simvastatin inhibits secretion of Th17-polarizing cytokines and antigen presentation by DCs in patients with relapsing remitting multiple sclerosis.Eur J Immunol 43, no. 1 (January 2013): 281–89. https://doi.org/10.1002/eji.201242566.
Zhang, Xin, et al. “Simvastatin inhibits secretion of Th17-polarizing cytokines and antigen presentation by DCs in patients with relapsing remitting multiple sclerosis.Eur J Immunol, vol. 43, no. 1, Jan. 2013, pp. 281–89. Pubmed, doi:10.1002/eji.201242566.
Journal cover image

Published In

Eur J Immunol

DOI

EISSN

1521-4141

Publication Date

January 2013

Volume

43

Issue

1

Start / End Page

281 / 289

Location

Germany

Related Subject Headings

  • Young Adult
  • Th17 Cells
  • Th1-Th2 Balance
  • Th1 Cells
  • Simvastatin
  • Multiple Sclerosis, Relapsing-Remitting
  • Monocytes
  • Middle Aged
  • Male
  • Lymphocyte Activation