Activation of human valve interstitial cells by a viridians streptococci modulin induces chemotaxis of mononuclear cells.
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.
Shun
Chia-Tung
CT
Departments of Forensic Medicine, National Taiwan University Hospital, Taipei, Taiwan, Republic of China.
Yeh
Chiou-Yueh
CY
Chang
Chia-Jung
CJ
Wu
Shu-Hui
SH
Lien
Huei-Ting
HT
Chen
Jen-Yang
JY
Wang
Shoei-Shen
SS
Chia
Jean-San
JS