| Project/Area Number |
15590379
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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 |
Bacteriology (including Mycology)
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| Research Institution | Hirosaki University |
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Principal Investigator |
HU Dong-liang Hirosaki University, School of Medicine, Lecturer, 医学部, 講師 (10333733)
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| Co-Investigator(Kenkyū-buntansha) |
NAKANE Akio Hirosaki University, School of Medicine, Professor, 医学部, 教授 (30164239)
WAKUI Makoto Hirosaki University, School of Medicine, Professor, 医学部, 教授 (80108505)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2004: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2003: ¥2,500,000 (Direct Cost: ¥2,500,000)
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| Keywords | staphylococcal enterotoxin / emetic activity / calcium / intestinal cell / NOS / カルシウム / サイトカイン / iNos / eNOS |
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| Research Abstract |
Staphylococcal enterotoxins (SEs) are exotoxic proteins produced by Staphylococcus aureus that cause staphylococcal food poisoning and toxic shock syndrome in humans and other species. However, the pathogenesis of SEs-mediated food poisoning, which causes diarrhea and vomiting within about 4-6 h of ingesting contaminated food, is not clearly understood.
In this study, we constructed and expressed mutants of SEA and investigated emetic and superantigenic activity of these mutant SEAs. Furthermore, to clarify whether SEA can affect any changes of cellular signalling pathways in intestinal epithelial cells, we performed experiments to see if SEA can modulate the intracellular signaling pathway in intestinal epithelial cells. Our results demonstrated for the first time that staphylococcal enterotoxin A (SEA) induces an increase in intracellular calcium ([Ca^<2+>]i) in human intestinal epithelial cells and the [Ca^<2+>]i is released from intracellular stores. SEA-induced increase of [Ca^<2+>]i was clearly inhibited by treatment with a nitric oxide synthase (NOS) inhibitor, N^G-monomethyl-L-arginine. Intestinal epithelial cells express endothelial NOS in resting cell condition, and express inducible NOS after stimulating with tumor necrosis factor (TNF)-α. TNF-α-pretreated cells showed a significant increase in [Ca^<2+>]i that was also inhibited by the NOS inhibitor. These results suggest that SEA modulated [Ca^<2+>]i signal is dependent on NOS expression in human intestinal epithelial cells.
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