This Article Full Text Full Text (PDF) Data Supplement All Versions of this Article: 92/10/1130    most recent 01.RES.0000074001.46892.1Cv1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Vielma, S. A. Articles by Lopes-Virella, M. F. Search for Related Content PubMed PubMed Citation Articles by Vielma, S. A. Articles by Lopes-Virella, M. F. Pubmed/NCBI databases Gene GEO Profiles HomoloGene UniGene Compound via MeSH Substance via MeSH Hazardous Substances DB 2-PHENYLETHANOL Related Collections Pathophysiology Risk Factors Cell signalling/signal transduction Endothelium/vascular type/nitric oxide

(Circulation Research. 2003;92:1130.)
© 2003 American Heart Association, Inc.

Cellular Biology

Chlamydophila pneumoniae Induces ICAM-1 Expression in Human Aortic Endothelial Cells via Protein Kinase C–Dependent Activation of Nuclear Factor-B

Silvana A. Vielma, Gregor Krings, Maria F. Lopes-Virella

From the Department of Microbiology and Immunology (S.A.V.), Graduate Program in Molecular and Cellular Biology and Pathobiology (G.K.), and Division of Endocrinology-Metabolism-Nutrition (M.F.L.-V.), Medical University of South Carolina, and Ralph H. Johnson VA Medical Center (M.F.L.-V.), Charleston, SC.

Correspondence to Maria F. Lopes-Virella, MD, PhD, Ralph H. Johnson VA Medical Center and Medical University of South Carolina, Strom Thurmond Research Building, 114 Doughty St, Charleston, SC 29425. E-mail virellam{at}musc.edu

Chlamydophila pneumoniae has an epidemiological link with atherosclerosis and acute cardiovascular events. One mechanism that may explain such a link is the increased expression of intracellular adhesion molecule-1 (ICAM-1) in C pneumoniae–infected endothelial cells. Upregulation of ICAM-1 by C pneumoniae is well recognized and has been extensively studied, but the signaling pathways involved are not yet defined. Because upregulation of ICAM-1 by cytokines and other stimuli has been shown to be mediated by either mitogen-activated protein kinase, protein kinase C (PKC), or nuclear factor-B (NF-B) pathways, we examined whether these pathways were involved in the ICAM-1 upregulation induced by C pneumoniae. Our data show a time-dependent phosphorylation of p44/p42 and SAPK/JNK pathways in C pneumoniae–infected cells. However, inhibition of the classic mitogen-activated protein kinase pathway using the PD98059 and U0126 inhibitors and inhibition of SAPK/JNK pathway did not suppress C pneumoniae–induced ICAM-1 expression. C pneumoniae also activates the NF-B pathway at 30 minutes after infection. Treatment of human aortic endothelial cells (HAECs) with the NF-B inhibitors BAY117085 and caffeic acid phenethyl ester led to a concentration-dependent inhibition of C pneumoniae–induced ICAM-1 upregulation. Finally, C pneumoniae–infected HAECs show membrane translocation of total PKC 30 minutes after cell infection. Calphostin C, a general PKC inhibitor, blocked both C pneumoniae–induced ICAM-1 expression and C pneumoniae–induced NF-B translocation. In conclusion, we demonstrated that C pneumoniae–induced ICAM-1 expression in HAECs requires NF-B and PKC activation and that NF-B activation is PKC dependent.

Key Words: Chlamydophila pneumoniae • intercellular adhesion molecule-1 • nuclear factor-B • protein kinase C • mitogen-activated protein kinase pathway

This article has been cited by other articles:

				R. Magid and P. F. Davies Endothelial Protein Kinase C Isoform Identity and Differential Activity of PKC{zeta} in an Athero-Susceptible Region of Porcine Aorta Circ. Res., September 2, 2005; 97(5): 443 - 449. [Abstract] [Full Text] [PDF]

				K. Hishikawa, T. Nakaki, and T. Fujita Oral Flavonoid Supplementation Attenuates Atherosclerosis Development in Apolipoprotein E-Deficient Mice Arterioscler Thromb Vasc Biol, February 1, 2005; 25(2): 442 - 446. [Abstract] [Full Text] [PDF]

				K. V. RAMANA, A. BHATNAGAR, and S. K. SRIVASTAVA Inhibition of aldose reductase attenuates TNF-{alpha}-induced expression of adhesion molecules in endothelial cells FASEB J, August 1, 2004; 18(11): 1209 - 1218. [Abstract] [Full Text] [PDF]

				S. A. Vielma, M. Mironova, J.-R. Ku, and M. F. Lopes-Virella Oxidized LDL further enhances expression of adhesion molecules in Chlamydophila pneumoniae-infected endothelial cells J. Lipid Res., May 1, 2004; 45(5): 873 - 880. [Abstract] [Full Text] [PDF]

				C. Y. Hong, J. H. Park, R. S. Ahn, S. Y. Im, H.-S. Choi, J. Soh, S. H. Mellon, and K. Lee Molecular Mechanism of Suppression of Testicular Steroidogenesis by Proinflammatory Cytokine Tumor Necrosis Factor Alpha Mol. Cell. Biol., April 1, 2004; 24(7): 2593 - 2604. [Abstract] [Full Text] [PDF]

				S.-W. Ryoo, D.-U. Kim, M. Won, K.-S. Chung, Y.-J. Jang, G.-T. Oh, S.-K. Park, P.-J. Maeng, H.-S. Yoo, and K.-L. Hoe Native LDL induces interleukin-8 expression via H2O2, p38 Kinase, and activator protein-1 in human aortic smooth muscle cells Cardiovasc Res, April 1, 2004; 62(1): 185 - 193. [Abstract] [Full Text] [PDF]