Fimbria-dependent activation of pro-inflammatory molecules in Porphyromonas gingivalis infected human aortic endothelial cells

doi:10.1111/j.1462-5822.2005.00661.x

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Wiley InterScience

Cellular Microbiology

Volume 8 Issue 5, Pages 738 - 757

Published Online: 8 Dec 2005

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Fimbria-dependent activation of pro-inflammatory molecules in Porphyromonas gingivalis infected human aortic endothelial cells

Yusuke Takahashi ^1,2 ^† , Michael Davey ³ ^† , Hiromichi Yumoto, ^1,4 Frank C. Gibson III ¹ and Caroline Attardo Genco ^1,3,5 *

¹ Department of Medicine, Section of Infectious Diseases, Boston University School of Medicine, Evans Biomedical Research Center, 650 Albany Street, Boston, MA 02218, USA. ² Department of Oral Microbiology, Kanagawa Dental College, 82 Inaokoa-cho, Yokosuka 238-8580, Japan. ³ Department of Periodontology and Oral Biology, Goldman School of Dental Medicine, Boston University, 100 East Newton Street, Boston, MA 02118, USA. ⁴ Department of Conservative Dentistry, Tokushima University School of Dentistry, 3-18-15 Kuramoto-cho Tokushima 770-8504, Japan. ⁵ Department of Microbiology, Boston University School of Medicine, 715 Albany Street, L-504, Boston, MA 02118, USA.

Correspondence to *E-mail Caroline.Genco@bmc.org; Tel. (+1) 617 414 5305; Fax (+1) 617 414 5280.

^† Both authors contributed equally to this body of work.

ABSTRACT

Epidemiological studies support that chronic periodontal infections are associated with an increased risk of cardiovascular disease. Previously, we reported that the periodontal pathogen Porphyromonas gingivalis accelerated atherosclerotic plaque formation in hyperlipidemic apoE^–/– mice, while an isogenic fimbria-deficient (FimA-) mutant did not. In this study, we utilized 41 kDa (major) and 67 kDa (minor) fimbria mutants to demonstrate that major fimbria are required for efficient P. gingivalis invasion of human aortic endothelial cells (HAEC). Enzyme-linked immunosorbent assay (ELISA) revealed that only invasive P. gingivalis strains induced HAEC production of pro-inflammatory molecules interleukin (IL)-1β, IL-8, monocyte chemoattractant protein (MCP)-1, intracellular adhesion molecule (ICAM)-1, vascular cellular adhesion molecule (VCAM)-1 and E-selectin. The purified native forms of major and minor fimbria induced chemokine and adhesion molecule expression similar to invasive P. gingivalis, but failed to elicit IL-1β production. In addition, the major and minor fimbria-mediated production of MCP-1 and IL-8 was inhibited in a dose-dependent manner by P. gingivalis lipopolysaccharide (LPS). Both P. gingivalis LPS and heat-killed organisms failed to stimulate HAEC. Treatment of endothelial cells with cytochalasin D abolished the observed pro-inflammatory MCP-1 and IL-8 response to invasive P. gingivalis and both purified fimbria, but did not affect P. gingivalis induction of IL-1β. These results suggest that major and minor fimbria elicit chemokine production in HAEC through actin cytoskeletal rearrangements; however, induction of IL-1β appears to occur via a separate mechanism. Collectively, these data support that invasive P. gingivalis and fimbria stimulate endothelial cell activation, a necessary initial event in the development of atherogenesis.