Abstract
We recently showed that FliC of Salmonella enteritidis increased human beta-defensin-2 (hBD-2) expression, and now describe the signaling responsible pathway. FliC increased the intracellular Ca(2+) concentration ([Ca(2+)](in)) in Caco-2 cells. The [Ca(2+)](in) increase induced by FliC was prevented by U73122 and heparin, but not by chelating extracellular Ca(2+) or pertussis toxin. The FliC-induced increase in hBD-2 promoter activity via nuclear factor kappaB (NF-kappaB) was also inhibited by chelation of intracellular Ca(2+) or by U73122. We conclude that FliC increased [Ca(2+)](in) via inositol 1,4,5-trisphosphate, which was followed by up-regulating hBD-2 mRNA expression via an NF-kappaB-dependent pathway.
MeSH terms
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Caco-2 Cells
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Calcium / metabolism
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Cell Nucleus / metabolism
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Chelating Agents / pharmacology
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Colon / metabolism
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Culture Media
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Egtazic Acid / pharmacology
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Estrenes / pharmacology
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Flagellin / pharmacology*
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Heparin / pharmacology
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Humans
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Inositol 1,4,5-Trisphosphate / metabolism
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Intestinal Mucosa / metabolism*
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NF-kappa B / metabolism
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Pertussis Toxin
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Promoter Regions, Genetic
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Pyrrolidinones / pharmacology
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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Salmonella enteritidis*
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Signal Transduction
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Up-Regulation
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Virulence Factors, Bordetella / pharmacology
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beta-Defensins / biosynthesis*
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beta-Defensins / genetics*
Substances
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Chelating Agents
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Culture Media
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DEFB4A protein, human
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Estrenes
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NF-kappa B
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Pyrrolidinones
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RNA, Messenger
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Virulence Factors, Bordetella
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beta-Defensins
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1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione
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Flagellin
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Egtazic Acid
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Inositol 1,4,5-Trisphosphate
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Heparin
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Pertussis Toxin
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Calcium