Mechanisms of Activation of Human Umbilical Vein Endothelial Cells by Viridans Streptococcal Glucosyltransferase
Date Issued
2007
Date
2007
Author(s)
Chen, Shih-Yi
DOI
zh-TW
Abstract
Infective endocarditis is a cardiovascular pathology that is often caused by bacteria.Viridans streptococci are major pathogens and Streptococcus mutans is the only member with its whole genomic sequence completed. Therefore, we focused on the investigation of virulence factors in S. mutans. We have identified previously that S. mutans, glucosyltransferase GTFC, induces endothelial cells activation to produce IL-6 and the activation could be blocked by pre-treatment of endothelial cells with cytochalasinD, a cellular skeleton inhibitor. This finding led us to hypothesize that GTFC may be internalized by endothelial cells to trigger an inflammatory responses through reactive oxygen species. Because, recent studies suggested that low concentrations of ROS in endothelial cells could induce inflammatory responses.Different inhibitors of endocytosis were tested to define whether caveolae- or clathrin-dependent pathway is associated with the internalization of GTFC. A clathrin-dependent inhibitor, MDC inhibited parally the production of IL-6, whereas the caveolae-related inhibitor, MβCD, failed to inhibit the GTFC induced cellular activation. Protein co-localization analysis by immunostaining indicated that GTFC could associate with clathrin but not caveolin-1, a finding correlated with that of inhibition analysis. GTFC could also co-localize with an early endosomal marker EEA1, further suggesting that clathrin-mediated endocytosis might be involved in GTFC internalization. Moreover, intracellular production of ROS, detected by H2DCFDA, was enhanced shortly after GTFC stimulation and ROS production could be inhibited by a NADPH oxidase inhibitor, apocynin, but not by an eNOS inhibitor, L-NMMA. Cellular signaling pathways involved in the GTFC-stimulated ROS production and subsequent activation were discussed.
Subjects
轉糖鏈球菌
葡萄糖傳遞酶
內皮細胞
內吞作用
活性氧分子
S. mutans
glucosyltransferase
endothelial cells
endocytosis
ROS
Type
other
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