Molecular mechanisms underlying human beta-defensin-2 gene expression in a human airway cell line (LC2/ad).
OBJECTIVE
Recently, human beta-defensin-2 (hBD-2), an inducible defensin, has been reported to be involved in innate immunity and host defence. To examine the exact roles of hBD-2 in the respiratory system, we examined the molecular mechanisms of hBD-2 gene expression in vitro.


METHODS
Using a human airway cell line (LC-2/ad), lipopolysaccharide (LPS)-induced gene expression of hBD-2 was studied in the absence or the presence of (i) dexamethasone, (ii) inhibition of NF-kappaB and AP-1, (iii) intracellular calcium chelator, and (iv) cyclooxygenase (COX) inhibitors.


RESULTS
Lipopolysaccharide-induced gene expression of hBD-2 was down-regulated by (i) dexamethasone, (ii) inhibition of NF-kappaB and AP-1, and (iii) intracellular calcium chelator. However, COX inhibitors had no effect on LPS-induced mRNA expression of hBD-2.


CONCLUSIONS
These findings suggest that glucocorticoids (GC), but not COX inhibitors, reduce hBD-2 gene expression, while NF-kappaB, AP-1 and intracellular calcium are essential for hBD-2 expression. Glucocorticoid-induced down-regulation of hBD-2 might be involved in the GC-induced suppression of respiratory host defence associated with hBD-2.
Tomita
Tetsuji
T
Department of Geriatric Medicine, Graduate School of Medicine, University of Tokyo, Tokyo, Japan. tomita-tky@umin.ac.jp
Nagase
Takahide
T
Ohga
Eijiro
E
Yamaguchi
Yasuhiro
Y
Yoshizumi
Masao
M
Ouchi
Yasuyoshi
Y
D015152:Blotting, Northern; D002118:Calcium / Q000502:physiology; D002460:Cell Line; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D015536:Down-Regulation; D015870:Gene Expression; D005938:Glucocorticoids / Q000494:pharmacology; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D016328:NF-kappa B / Q000502:physiology; D012137:Respiratory System / Q000166:cytology / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000502:physiology; D023083:beta-Defensins / Q000235:genetics*
D016861:Cyclooxygenase Inhibitors; C106641:DEFB4A protein, human; D005938:Glucocorticoids; D008070:Lipopolysaccharides; D016328:NF-kappa B; D014157:Transcription Factors; D023083:beta-Defensins; D003907:Dexamethasone; D002118:Calcium