2006 Fiscal Year Final Research Report Summary
Roles of chlamydial lipopoly saccharide and innate immune responses in atherogenesis
| Project/Area Number |
17590763
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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 |
Circulatory organs internal medicine
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| Research Institution | Juntendo University |
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Principal Investigator |
ISHII Yuko Juntendo University, School of Medicine, Research Associate (00251546)
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| Co-Investigator(Kenkyū-buntansha) |
MIYAUCHI Katsumi JUNTENDO UNIVERSITY, School of Medicine, Associate Professor (60200119)
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| Project Period (FY) |
2005 – 2006
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| Keywords | Atherosclerosis / Chlamydiaceae / Lipopolysaccharide(LPS) / immune response / moflonaclear cells / low density ltpoprotein(LDL) / CD14 / Toll-tike receptor(TLR) |
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| Research Abstract |
Chlamydiaceae are small obligate intracellular parasites and classified as gram-negative bacteria. Although recent studies have suggested that chronic inflammatory reactions by Chlamydophila pneumoniae is associated with the development of atherosclerosis, little is known about the mechanisms for Chlamydiaceae -induced host cell activation.
Among Chlamydiaceae-derived components, LPS is known as a potent immunomodulator, and chlamydial LPS possesses a unique lipid A structure with longer but less acyl chains. In this study, to elucidate the chlamydial LPS-induced immune responses, we evaluated the actions of chlamydial LPS on human PBMC, using Chlamydophila psittaci LPS whose structure is nearly identical to that of C. pneumoniae, and compared with those of E. coli LPS.
Similar to E. coli LPS, C. psittaci LPS bound to monocytes and induced the pro-inflammatory cytokine production in an LPS-binding protein (LBP)-dependent manner. However, C. psittaci LPS was much less potent than E. coli
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LPS in both the LPS binding and cytokine production. Interestingly, the binding of C. psittaci LPS was mediated by CD14, TLR4 and CD11b, whereas the cytokine production was dependent on CD14 and TLR4 but not CD11b. Of note, ELIS A-based binding assays revealed that C. psittaci LPS directly bound to LBP and CD14; however the affinities were much less man those of E. coli LPS. Together, these observations possibly suggest that Chlamydiaceae LPS has low binding affinities for LPS-recognition molecules such as CD14 and LBP, and exhibit weak biological activities against host immune cells including monocytes, thereby contributing to the chronic (persistent) inflammatory reactions during infection. Together, these observations indicate that chlamydial LPS has the low binding affinities for LPS-recognition molecules, and exhibits weak biological activities against host immune cells such as monocytes, thereby contributing to the chronic (persistent) inflammatory reactions during chlamydial infection. Less
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