TATEDA K, ISHII Y, HORIKAWA M, ISHIGURO M, YAMAGUCHI K; Interscience Conference on Antimicrobial Agents and Chemotherapy (43rd: 2003: Chicago, Ill.).
Abstr Intersci Conf Antimicrob Agents Chemother Intersci Conf Antimicrob Agents Chemother. 2003 Sep 14-17; 43: abstract no. B-1050.
Toho University School of Medicine, Tokyo, Japan.
BACKGROUND: Las and Rhl are two major quorum-sensing components of Pseudomonas aeruginosa, and these are regulated by their corresponding autoinducers, N-3-oxododecanoyl homoserine lactone (C[12]-HSL) and N-butyryl-L-homoserine lactone (C[4]-HSL). The recent progress demonstrated potential of quorum-sensing molecules, especially C[12]-HSL, in modulating host immune system. Here we show specific activity of C[12]-HSL to induce apoptosis in certain types of cells. METHODS: Pseudomonas autoinducers were chemically synthesized. Several cell lines and bone marrow-derived macrophages (BM-Mf from C57BL/6 mice were used in this study. Apoptosis was acessed by multiple criterias (caspase activity, histone-DNA, annexin-V/PI). RESULTS: When BM-Mf were incubated with C[12]-HSL, but not C[4]-HSL, significant loss of viability was observed in a concentration (12-50 micro-M) and incubation time-dependent manner (1-24 h). The cytotoxic activity of C[12]-HSL was also observed in neutrophils, monocytic cell lines U-937 and P388D1, but not in epithelial cell lines CCL-185 and HEp-2. Cells treated with C[12]-HSL revealed morphologic alterations of the cells indicative for apoptosis. Acceleration of apoptosis in C[12]-HSL-treated cells was confirmed by increase of caspase-3, -8 activities, histone-associated DNA fragments and phosphatidylserine expression by flow-cytometry. The structure-activity correlation experiments demonstrated that fine structures of C[12]-HSL, in addition to HSL-backbone and length of side chain, were required for maximal activity. CONCLUSIONS: These data suggests that Pseudomonas C[12]-HSL specifically promote induction of apoptosis in certain types of cells. Our data suggest critical roles of quorum-sensing molecule C[12]-HSL in the pathogenesis of P. aeruginosa infection, not only through induction of bacterial virulence factors, but also modulation of host responses.
Publication Types:
Keywords:
- 4-Butyrolactone
- Animals
- Apoptosis
- Cell Line
- Chromosomes
- Epithelial Cells
- Macrophages
- Mice
- Mice, Inbred C57BL
- Neutrophils
- Pseudomonas aeruginosa
- Transcription, Genetic
- genetics
- homoserine lactone
Other ID:
UI: 102265561
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