Activation of human valvular fibroblasts byglucosyltransferases of viridans streptococci to induce chemotaxis of leukocytes
碩士 === 國立臺灣大學 === 口腔生物科學研究所 === 95 === Streptococcus mutans is a member of viridans group streptococci and one of the opportunistic pathogens causing subacute infective endocarditis (IE). The major process in the pathogenesis of IE is initiated when pathogens circulating in the bloodstream colonize...
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ndltd-TW-095NTU055960052015-12-07T04:04:13Z http://ndltd.ncl.edu.tw/handle/54744211749269320086 Activation of human valvular fibroblasts byglucosyltransferases of viridans streptococci to induce chemotaxis of leukocytes 人類心臟瓣膜纖維母細胞受草綠色鏈球菌葡萄糖傳遞酶活化引發白血球趨化作用之研究 Chia-Jung Chang 張家榮 碩士 國立臺灣大學 口腔生物科學研究所 95 Streptococcus mutans is a member of viridans group streptococci and one of the opportunistic pathogens causing subacute infective endocarditis (IE). The major process in the pathogenesis of IE is initiated when pathogens circulating in the bloodstream colonize to damaged valves and then secrete virulence factors to induce a chronic inflammatory response. Glucosyltransferases (GTFs) of viridans streptococci are the important bacterial modulins and potent inducers of interleukin-6 (IL-6) synthesis and release from human PBMC and HUVEC. Because the heart valves were constituted primary by meshes of fibroblasts, we investigated the primary culture of valvular fibroblasts from heart transplant patients to study the immune response stimulated by GTFs and to define the mechanism of IE triggered by the viridans streptococci. We reported that GTFs attached to human primary valvular fibroblasts triggered the release of IL-6, IL-8 and MCP-1, and enhanced the phosphorylation of AKT, MAPKs and IκB-α and the nuclear translocation of NF-κB. The increase in IL-6, IL-8 and MCP-1 was abrogated by addition of PI3K, MAPKs, and NF-κB inhibitors, suggesting that the up-regulation of IL-6, IL-8 and MCP-1 was mediated through PI3K, MAPKs, and NF-κB signaling pathways. We also demonstrated that valvular fibroblasts treated by GTFs promoted the chemotaxis and adhesion of monocytic cell lines. In addition, GTFs-stimulated valvular fibroblasts could induce the release of CXCR4-specific ligand to enhance the recruitment of T lymphocyte. Because GTFs could stimulate human mononuclear cells to produce interleukin-1β(IL-1β), we hypothesized that the infiltration of GTFs-activated mononuclear cells could play a role in enhancing inflammatory response. We found that exogenous IL-1β could activate valvular fibroblasts, trigger the release of IL-6, IL-8 and MCP-1, and up-regulate the expression of ICAM-1. In addition, IL-1β-stimulated fibroblasts could promote the chemotaxis and adhesion of monocytic cell lines. Taken together, these results indicate that GTFs could induce the synthesis and release of inflammatory cytokine and chemokine to trigger the infiltration of leukocytes a characteristic in the pathogenesis of IE caused by viridans group streptococci. Furthermore, GTFs-activated mononuclear cells could secrete IL-1β to further stimulate valvular fibroblasts and sustain the formation of chronic endocardial inflammation. 賈景山 2007 學位論文 ; thesis 67 zh-TW |
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碩士 === 國立臺灣大學 === 口腔生物科學研究所 === 95 === Streptococcus mutans is a member of viridans group streptococci and one of the opportunistic pathogens causing subacute infective endocarditis (IE). The major process in the pathogenesis of IE is initiated when pathogens circulating in the bloodstream colonize to damaged valves and then secrete virulence factors to induce a chronic inflammatory response. Glucosyltransferases (GTFs) of viridans streptococci are the important bacterial modulins and potent inducers of interleukin-6 (IL-6) synthesis and release from human PBMC and HUVEC. Because the heart valves were constituted primary by meshes of fibroblasts, we investigated the primary culture of valvular fibroblasts from heart transplant patients to study the immune response stimulated by GTFs and to define the mechanism of IE triggered by the viridans streptococci.
We reported that GTFs attached to human primary valvular fibroblasts triggered the release of IL-6, IL-8 and MCP-1, and enhanced the phosphorylation of AKT, MAPKs and IκB-α and the nuclear translocation of NF-κB. The increase in IL-6, IL-8 and MCP-1 was abrogated by addition of PI3K, MAPKs, and NF-κB inhibitors, suggesting that the up-regulation of IL-6, IL-8 and MCP-1 was mediated through PI3K, MAPKs, and NF-κB signaling pathways. We also demonstrated that valvular fibroblasts treated by GTFs promoted the chemotaxis and adhesion of monocytic cell lines. In addition, GTFs-stimulated valvular fibroblasts could induce the release of CXCR4-specific ligand to enhance the recruitment of T lymphocyte.
Because GTFs could stimulate human mononuclear cells to produce interleukin-1β(IL-1β), we hypothesized that the infiltration of GTFs-activated mononuclear cells could play a role in enhancing inflammatory response. We found that exogenous IL-1β could activate valvular fibroblasts, trigger the release of IL-6, IL-8 and MCP-1, and up-regulate the expression of ICAM-1. In addition, IL-1β-stimulated fibroblasts could promote the chemotaxis and adhesion of monocytic cell lines.
Taken together, these results indicate that GTFs could induce the synthesis and release of inflammatory cytokine and chemokine to trigger the infiltration of leukocytes a characteristic in the pathogenesis of IE caused by viridans group streptococci. Furthermore, GTFs-activated mononuclear cells could secrete IL-1β to further stimulate valvular fibroblasts and sustain the formation of chronic endocardial inflammation.
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author2 |
賈景山 |
author_facet |
賈景山 Chia-Jung Chang 張家榮 |
author |
Chia-Jung Chang 張家榮 |
spellingShingle |
Chia-Jung Chang 張家榮 Activation of human valvular fibroblasts byglucosyltransferases of viridans streptococci to induce chemotaxis of leukocytes |
author_sort |
Chia-Jung Chang |
title |
Activation of human valvular fibroblasts byglucosyltransferases of viridans streptococci to induce chemotaxis of leukocytes |
title_short |
Activation of human valvular fibroblasts byglucosyltransferases of viridans streptococci to induce chemotaxis of leukocytes |
title_full |
Activation of human valvular fibroblasts byglucosyltransferases of viridans streptococci to induce chemotaxis of leukocytes |
title_fullStr |
Activation of human valvular fibroblasts byglucosyltransferases of viridans streptococci to induce chemotaxis of leukocytes |
title_full_unstemmed |
Activation of human valvular fibroblasts byglucosyltransferases of viridans streptococci to induce chemotaxis of leukocytes |
title_sort |
activation of human valvular fibroblasts byglucosyltransferases of viridans streptococci to induce chemotaxis of leukocytes |
publishDate |
2007 |
url |
http://ndltd.ncl.edu.tw/handle/54744211749269320086 |
work_keys_str_mv |
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