GroEL1, from Chlamydia pneumoniae, induces vascular adhesion molecule 1 expression by p37(AUF1) in endothelial cells and hypercholesterolemic rabbit.
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.
Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
Chun-Yao
CY
Huang
Chun-Ming
CM
Shih
Nai-Wen
NW
Tsao
Yung-Hsiang
YH
Chen
Chi-Yuan
CY
Li
Yu-Jia
YJ
Chang
Nen-Chung
NC
Chang
Keng-Liang
KL
Ou
Cheng-Yen
CY
Lin
Yi-Wen
YW
Lin
Chih-Hao
CH
Nien
Feng-Yen
FY
Lin
D020121:5' Untranslated Regions; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism; D050197:Atherosclerosis / Q000235:genetics / Q000378:metabolism; D002417:Cattle; D002460:Cell Line; D018834:Chaperonin 60 / Q000378:metabolism* / Q000494:pharmacology; D016993:Chlamydophila pneumoniae / Q000378:metabolism*; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D000081035:Heterogeneous Nuclear Ribonucleoprotein D0; D034502:Heterogeneous-Nuclear Ribonucleoprotein D / Q000378:metabolism*; D006937:Hypercholesterolemia / Q000235:genetics* / Q000378:metabolism*; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D008297:Male; D020871:RNA Stability / Q000187:drug effects; D011817:Rabbits; D011994:Recombinant Proteins / Q000378:metabolism / Q000494:pharmacology; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics* / Q000378:metabolism
D020121:5' Untranslated Regions; D018834:Chaperonin 60; C000630986:HNRNPD protein, human; D000081035:Heterogeneous Nuclear Ribonucleoprotein D0; D034502:Heterogeneous-Nuclear Ribonucleoprotein D; D011994:Recombinant Proteins; D019010:Vascular Cell Adhesion Molecule-1