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Infection and Immunity, February 2006, p. 1273-1283, Vol. 74, No. 2
0019-9567/06/$08.00+0     doi:10.1128/IAI.74.2.1273-1283.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Glucosyltransferases of Viridans Group Streptococci Modulate Interleukin-6 and Adhesion Molecule Expression in Endothelial Cells and Augment Monocytic Cell Adherence

Chiou-Yueh Yeh,1 Jen-Yang Chen,1,2 and Jean-San Chia1,3*

Graduate Institute of Microbiology, College of Medicine, National Taiwan University,1 National Health Research Institute,2 Department of Dentistry, National Taiwan University Hospital, Taipei, Taiwan, Republic of China3

Received 6 September 2005/ Returned for modification 28 October 2005/ Accepted 11 November 2005

Recruitment of monocytes plays important roles during vegetation formation and endocardial inflammation in the pathogenesis of infective endocarditis (IE). Bacterial antigens or modulins can activate endothelial cells through the expression of cytokines or adhesion molecules and modulate the recruitment of leukocytes. We hypothesized that glucosyltransferases (GTFs), modulins of viridans group streptococci, may act directly to up-regulate the expression of adhesion molecules and also interleukin-6 (IL-6) to augment monocyte attachment to endothelial cells. Using primary cultured human umbilical vein endothelial cells (HUVECs) as an in vitro model, we demonstrated that GTFs (in the cell-bound or free form) could specifically modulate the expression of IL-6, and also adhesion molecules, in a dose- and time-dependent manner. Results of inhibition assays suggested that enhanced expression of adhesion molecules was dependent on the activation of nuclear factor {kappa}B (NF-{kappa}B) and extracellular signal-regulated kinase and that p38 mitogen-activated protein kinase pathways also contributed to the release of IL-6. Streptococcus-infected HUVECs or treatment with purified IL-6 plus soluble IL-6 receptor {alpha} enhanced the expression of ICAM-1 and the adherence of the monocytic cell line U937. These results suggest that streptococcal GTFs might play an important role in recruiting monocytic cells during inflammation in IE through induction of adhesion molecules and IL-6, a cytokine involved in transition from neutrophil to monocyte recruitment.


* Corresponding author. Mailing address: No. 1, Jen Ai Road, 1st Section, Room 713, Graduate Institute of Microbiology, College of Medicine, National Taiwan University, Taipei, Taiwan. Phone: 886-2-23123456, ext. 8222. Fax: 886-2-23926238. E-mail: chiajs{at}ha.mc.ntu.edu.tw.

Editor: V. J. DiRita


Infection and Immunity, February 2006, p. 1273-1283, Vol. 74, No. 2
0019-9567/06/$08.00+0     doi:10.1128/IAI.74.2.1273-1283.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.




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