title: Activation of human valve interstitial cells by a viridians streptococci modulin induces chemotaxis of mononuclear cells.
abstract: Infective endocarditis is characterized by inflammatory infiltrates of mononuclear cells in infected cardiac valve leaflets. To delineate the role of valve interstitial cells (VICs) in leukocyte recruitment, we stimulated human VICs with glucosyltransferase, a modulin from viridians streptococci. Interstitial cells were activated directly by glucosyltransferase in a dose-dependent manner through concerted mitogen-activated protein kinase and nuclear factor-kappaB signaling pathways; activation resulted in up-regulation of synthesis and release of interleukin-6, interleukin-8, or monocyte chemoattractant protein-1 and enhanced transwell migration of U937 monocytic cells or primary mononuclear cells. The expression of glucosyltransferases and activation of VICs (nuclear localization of RelA) were detected in a rat model of experimental endocarditis. Proinflammatory cytokines also were detected in VICs from diseased human autopsy specimens but not in VICs from normal specimens. These results indicate that interstitial cells in the cardiac valve can be activated directly by bacterial modulins to recruit and retain mononuclear cells, likely contributing to the persistent inflammation characteristic of infective endocarditis.
authors.affiliation: Departments of Forensic Medicine, National Taiwan University Hospital, Taipei, Taiwan, Republic of China.
authors.forename: Chia-Tung
authors.initials: CT
authors.lastname: Shun
authors.forename: Chiou-Yueh
authors.initials: CY
authors.lastname: Yeh
authors.forename: Chia-Jung
authors.initials: CJ
authors.lastname: Chang
authors.forename: Shu-Hui
authors.initials: SH
authors.lastname: Wu
authors.forename: Huei-Ting
authors.initials: HT
authors.lastname: Lien
authors.forename: Jen-Yang
authors.initials: JY
authors.lastname: Chen
authors.forename: Shoei-Shen
authors.initials: SS
authors.lastname: Wang
authors.forename: Jean-San
authors.initials: JS
authors.lastname: Chia