Hydroxymethylglutaryl coenzyme A reductase inhibition reduces Chlamydia pneumoniae-induced cell interaction and activation

Ralf Dechend*, Jens Gieffers, Rainer Dietz, Achim Joerres, Jan Rupp, Friedrich C. Luft, Matthias Maass

*Korrespondierende/r Autor/-in für diese Arbeit
57 Zitate (Scopus)

Abstract

Background - Chlamydia pneumoniae stimulates chronic inflammation in vascular cells. Hydroxymethylglutaryl coenzyme A reductase inhibitors (statins) may have an ameliorating effect. We investigated possible mechanisms. Methods and Results - We infected human macrophages that in coculture spread infection to vascular smooth muscle cells (VSMCs). Cerivastatin (250 nmol/L) reduced VSMC infection by 33%. Western blotting made it apparent that VSMC infection resulted in increased cell membrane-associated RhoA and Racl, implying increased prenylation of these proteins. This effect was blocked by statin but circumvented by mevalonate. Cytochrome C assays showed that infected VSMCs produced increased reactive oxygen species that was blocked by statin. Infection increased nuclear transcription factor-κB expression in VSMCs that was dose-dependently suppressed by statin. Infected VSMCs produced and released RANTES and MCP-1. Statin dose-dependently blocked this production both at the mRNA and protein levels. Mevalonate and M geranylgeranylpyrophosphate circumvented these effects. Conclusions - C pneumoniae can be transmitted from macrophages to VSMCs. VSMCs showed an activation profile typical of atherosclerosis, namely Rac1 and RhoA prenylation, nuclear transcription factor-κB activation, reactive oxygen species production, and chemokine production. Statin reduces macrophage-mediated C pneumoniae-induced signaling and transmission.

OriginalspracheEnglisch
ZeitschriftCirculation
Jahrgang108
Ausgabenummer3
Seiten (von - bis)261-265
Seitenumfang5
ISSN0009-7322
DOIs
PublikationsstatusVeröffentlicht - 22.07.2003

Strategische Forschungsbereiche und Zentren

  • Forschungsschwerpunkt: Infektion und Entzündung - Zentrum für Infektions- und Entzündungsforschung Lübeck (ZIEL)

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