Production of beta-defensin-2 by human colonic epithelial cells induced by Salmonella enteritidis flagella filament structural protein.
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.
Takahashi
A
A
Department of Nutrition, School of Medicine, University of Tokushima, Japan. akiratak@nutr.med.tokushima-u.ac.jp
Wada
A
A
Ogushi
K
K
Maeda
K
K
Kawahara
T
T
Mawatari
K
K
Kurazono
H
H
Moss
J
J
Hirayama
T
T
Nakaya
Y
Y
D018938:Caco-2 Cells; D002118:Calcium / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D002614:Chelating Agents / Q000494:pharmacology; D003106:Colon / Q000378:metabolism; D003470:Culture Media; D004533:Egtazic Acid / Q000494:pharmacology; D004963:Estrenes / Q000494:pharmacology; D005408:Flagellin / Q000494:pharmacology*; D006493:Heparin / Q000494:pharmacology; D006801:Humans; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D037342:Pertussis Toxin; D011401:Promoter Regions, Genetic; D011760:Pyrrolidinones / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012477:Salmonella enteritidis; D015398:Signal Transduction; D015854:Up-Regulation; D010566:Virulence Factors, Bordetella / Q000494:pharmacology; D023083:beta-Defensins / Q000096:biosynthesis* / Q000235:genetics*
D002614:Chelating Agents; D003470:Culture Media; C106641:DEFB4A protein, human; D004963:Estrenes; D016328:NF-kappa B; D011760:Pyrrolidinones; D012333:RNA, Messenger; D010566:Virulence Factors, Bordetella; D023083:beta-Defensins; C060229:1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione; D005408:Flagellin; D004533:Egtazic Acid; D015544:Inositol 1,4,5-Trisphosphate; D006493:Heparin; D037342:Pertussis Toxin; D002118:Calcium