2002 Fiscal Year Final Research Report Summary
Mechanism and inhibitors of Chlamydia trachomatis infection of eukaryotic host cells
| Project/Area Number |
12671639
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Obstetrics and gynecology
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| Research Institution | AICHI MEDICAL UNIVERSITY |
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Principal Investigator |
NOGUCHI Masayoshi Aichi Medical University, School of Medicine, Professor, 医学部, 教授 (80065557)
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| Co-Investigator(Kenkyū-buntansha) |
YABUSHITA Hiromitsu Aichi Medical University, School of Medicine, Assistant professor, 医学部, 助教授 (00140046)
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| Project Period (FY) |
2000 – 2002
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| Keywords | Heparan sulfate / proteoglycans / Chlamydia trachomatis / Chemically modified heparin / heparinase / chlamydial attachment |
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| Research Abstract |
The mechanism and inhibitors of Chlamydia trachomatis (C. trachomatis) serovar L2 infection of eukaryotic host cells were studied using a tissue culture model infection system. Potent inhibition of the infectivity was observed when elementary bodies (EBs) were exposed to heparin or when HeLa 229 cells were treated with heparinase. No significant inhibition was seen the other way around. The same potent inhibition was observed when EBs were exposed to chemically 2-O-desulfated heparin (2-ODS heparin) which is composed of repeating disaccharide units of IdoA-GlcNS(6S), but not when exposed to chemically 6-O-desulfated heparin (6-ODS heparin) or completely desulfated and N-resulfated heparin (CDSNS heparin) which is composed of repeating disaccharide units of IdoA(2S)-GlcNS or IdoA-GlcNS, respectively. The inhibitory effects of 2-ODS heparin could be seen with their oligosaccharides longer than dodecasaccharides. The mutant CHO cell line, 677, which is deficient in the biosynthesis of heparan sulfate, was less sensitive to the C. trachomatis infection than wild CHO cells. F-17 cells which is deficient in 2-O-sulfation of heparan sulfate had the same sensitivity to the infection as wild CHO cells did. These data suggest that the infection of EBs to host cells results from the specific binding of ligand molecules with affinity for heparin on the EB surface to the heparan sulfate proteoglycan receptors on the host cell surface. This binding may depend on the heparan sulfate chains of host cells which are 6-O-sulfated and longer than dodecasaccharides. The 2-ODS heparin oligosaccharides may be a potential agent for the prevention of C. trachomatis infection.
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[Publications] Yabushita, H., Shimazu, M., Noguchi, M., Kinoshita, S., Kishida, T., Narumiya, H., Sawaguchi, K., Noguchi, M: "Vascular endothelial growth factor activating matrix metalloproteinase in ascitic fluid during peritoneal dissemination of ovarian cancer"Oncol. Rep.. 10. 89-95 (2003)
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「研究成果報告書概要(欧文)」より
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[Publications] Noguchi, Y., Yabushita, H., Noguchi, M., Fajita, M., Asai, M., Del Carpio, C. A.: "Detection of Chlamydia trachomatis infection with DNA extracted from formalin-fixed paraffin-embedded tissues"Diag. Microbiol. Infect. Dis.. 43. 1-6 (2002)
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「研究成果報告書概要(欧文)」より
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[Publications] Yabushita, H., Noguchi, M., Narumiya, H., Sawaguchi, K., Noguchi, M: "Apoptosis in relation to p53, WAF1, bcl-2 and Bax expression in cervical intraepithelial neoplasia"J. Aichi Med. Univ. Assoc.. 30. 195-202 (2002)
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「研究成果報告書概要(欧文)」より
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[Publications] Yabushita, M., Noguchi, M., Kinoshita, S., Kishida, T., Sawaguchi, K., Noguchi, M: "Angiostatin expression in endometrial cancer"Oncol. Rep.. 9. 1193-1196 (2002)
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「研究成果報告書概要(欧文)」より
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[Publications] Yabushita, M., Noguchi, Y., Habuchi, H., Ashikari, S., Nakabe, K., Fujita, M., Noguchi, M., Esko, J. D., Kimata, K.: "Effects of chemically modified heparin on Chlamydia trachomatis serovar L2 infection of eukaryotic cells in culture"Glycobiology. 12. 345-351 (2002)
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「研究成果報告書概要(欧文)」より
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[Publications] Yabushita, H., Shimazu, M., Yamada, H., Sawaguchi, K., Noguchi, M., Nakanishi, M., Kawai, M.: "Occult lymph node metastases detected by cytokeratin immunohistochemistry predict recurrence in node-negative endometrial cancer"Gynecol. Oncol.. 80. 139-144 (2001)
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「研究成果報告書概要(欧文)」より
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[Publications] Yabushita, H., Narumiya, H., Hiratake, K., Yamada, H,. Shimazu, M., Sawaguchi, K., Noguchi, M., Nakanishi, M.: "The association of transforming growth factor-β1 with myometrial invasion of endometrial carcinomas through effects on matrix metalloproteinase"J Obstet. Gynecol.. 26(3). 163-170 (2000)
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「研究成果報告書概要(欧文)」より
