GroEL1, from Chlamydia pneumoniae, induces vascular adhesion molecule 1 expression by p37(AUF1) in endothelial cells and hypercholesterolemic rabbit

PLoS One. 2012;7(8):e42808. doi: 10.1371/journal.pone.0042808. Epub 2012 Aug 10.

Abstract

The expression of vascular adhesion molecule-1 (VCAM-1) by endothelial cells may play a major role in atherogenesis. The actual mechanisms of chlamydia pneumoniae (C. pneumoniae) relate to atherogenesis are unclear. We investigate the influence of VCAM-1 expression in the GroEL1 from C. pneumoniae-administered human coronary artery endothelial cells (HCAECs) and hypercholesterolemic rabbits. In this study, we constructed the recombinant GroEL1 from C. pneumoniae. The HCAECs/THP-1 adhesion assay, tube formation assay, western blotting, enzyme-linked immunosorbent assay, actinomycin D chase experiment, luciferase reporter assay, and immunohistochemical stainings were performed. The results show that GroEL1 increased both VCAM-1 expression and THP-1 cell adhesives, and impaired tube-formation capacity in the HCAECs. GroEL1 significantly increased the VCAM-1 mRNA stability and cytosolic AU-binding factor 1 (AUF1) level. Overexpression of the p37(AUF1) significantly increased VCAM-1 gene expression in GroEL1-induced bovine aortic endothelial cells (BAECs). GroEL1 prolonged the stability of VCAM-1 mRNA by increasing both p37(AUF1) and the regulation of the 5' untranslated region (UTR) of the VCAM-1 mRNA in BAECs. In hypercholesterolemic rabbits, GroEL1 administration enhanced fatty-streak and macrophage infiltration in atherosclerotic lesions, which may be mediated by elevated VCAM-1 expression. In conclusion, GroEL1 induces VCAM-1 expression by p37(AUF1) in endothelial cells and enhances atherogenesis in hypercholesterolemic rabbits.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 5' Untranslated Regions
  • Animals
  • Aorta / drug effects
  • Aorta / metabolism
  • Atherosclerosis / genetics
  • Atherosclerosis / metabolism
  • Cattle
  • Cell Line
  • Chaperonin 60 / metabolism*
  • Chaperonin 60 / pharmacology
  • Chlamydophila pneumoniae / metabolism*
  • Endothelial Cells / drug effects
  • Endothelial Cells / metabolism*
  • Gene Expression Regulation / drug effects
  • Heterogeneous Nuclear Ribonucleoprotein D0
  • Heterogeneous-Nuclear Ribonucleoprotein D / metabolism*
  • Hypercholesterolemia / genetics*
  • Hypercholesterolemia / metabolism*
  • Macrophages / immunology
  • Macrophages / metabolism
  • Male
  • RNA Stability / drug effects
  • Rabbits
  • Recombinant Proteins / metabolism
  • Recombinant Proteins / pharmacology
  • Vascular Cell Adhesion Molecule-1 / genetics*
  • Vascular Cell Adhesion Molecule-1 / metabolism

Substances

  • 5' Untranslated Regions
  • Chaperonin 60
  • HNRNPD protein, human
  • Heterogeneous Nuclear Ribonucleoprotein D0
  • Heterogeneous-Nuclear Ribonucleoprotein D
  • Recombinant Proteins
  • Vascular Cell Adhesion Molecule-1

Grants and funding

This work was funded partial by the National Science Council (NSC 99-2314-B-038-030-MY2) and Taiwan Department of Health Clinical Trial and Research Center of Excellence (DOH100-TD-B-111-004), Taiwan. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.