Lovastatin inhibits bone marrow-derived dendritic cell maturation and upregulates proinflammatory cytokine production

Dongxu Sun, Gabriel Fernandes

Research output: Contribution to journalArticle

47 Scopus citations

Abstract

Statins are a group of hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitors which are most effective as lipid lowering agents, and are currently extensively used clinically. Recently, it was also shown that statins affect the immune response. We investigated the effects of lovastatin on the maturation and functional changes of bone marrow-derived dendritic cells (BM-DC). Lovastatin inhibited MHC class II and CD40 expression on DC in a dose-dependent manner, but had lesser effects on CD16, CD80, CD86, and CD11b expression. Nuclear extracts of lovastatin treated DC had decreased NF-κB DNA binding activity. Although antigen capture capacity of DC was not affected by lovastatin, the T-cell stimulatory activity of DC was inhibited. Lovastatin up-regulated DC pro-inflammatory cytokine production induced by LPS as measured by intracellular cytokine staining, ELISA and cDNA microarrays. Mevalonate, added in vitro, prevented these effects. These results indicate that lovastatin may inhibit BM-DC maturation and up-regulate cytokine production through a mevalonate dependent pathway, and may cause adverse effects on either innate or adaptive immunity.

Original languageEnglish (US)
Pages (from-to)52-62
Number of pages11
JournalCellular Immunology
Volume223
Issue number1
DOIs
StatePublished - May 2003

    Fingerprint

Keywords

  • Dendritic cells
  • Immune response
  • Lovastatin
  • Statins

ASJC Scopus subject areas

  • Immunology

Cite this