Molecular mechanisms underlying human beta-defensin-2 gene expression in a human airway cell line (LC2/ad).

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. 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. 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. 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.