title: Differential effects of alpha- and beta-defensin on cytokine production by cultured human bronchial epithelial cells.
abstract: Defensins are cysteine-rich cationic antimicrobial peptides that play an important role in innate immunity and are known to contribute to the regulation of host adaptive immunity. In addition to direct antimicrobial activities, it has been recently reported that alpha-defensins, mainly present in neutrophils in the lung, have a cytotoxic effect and induce IL-8 production from airway epithelial cells. Although beta-defensins are expressed in epithelial cells in various tissues, including lung, there are no reports of their effects on cytokine synthesis in airway epithelial cells. The aim of the present study was to determine the effects of both alpha- and beta-defensins on the cytokine production, transcription factor binding activity, and cytotoxicity in primary cultured human bronchial epithelial cells (HBECs). We used human neutrophil peptide-1 (HNP-1; alpha-defensin) and human beta-defensin-2 (HBD-2) to stimulate HBECs. The results showed that treatment of HBECs with HNP-1, but not HBD-2, increased IL-8 and IL-1beta mRNA expression in a dose-dependent manner and also enhanced IL-8 protein secretion and NF-kappaB DNA binding activity. The 24-h treatments with >20 microg/ml of HNP-1 or >50 microg/ml of HBD-2 were cytotoxic to HBECs. These results suggest that alpha- and beta-defensins have different effects on cytokine synthesis by airway epithelial cells, and we speculate that they play different roles in inflammatory lung diseases.
authors.affiliation: Second Department of Internal Medicine, Nagasaki University School of Medicine, Sakamoto 1-7-1, Nagasaki 852-8501, Japan.
authors.forename: Noriho
authors.initials: N
authors.lastname: Sakamoto
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Mukae
authors.forename: Takeshi
authors.initials: T
authors.lastname: Fujii
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ishii
authors.forename: Sumako
authors.initials: S
authors.lastname: Yoshioka
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Kakugawa
authors.forename: Kanako
authors.initials: K
authors.lastname: Sugiyama
authors.forename: Yohei
authors.initials: Y
authors.lastname: Mizuta
authors.forename: Jun-ichi
authors.initials: J
authors.lastname: Kadota
authors.forename: Masamitsu
authors.initials: M
authors.lastname: Nakazato
authors.forename: Shigeru
authors.initials: S
authors.lastname: Kohno
mesh_terms: D001980:Bronchi / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D023084:alpha-Defensins / Q000494:pharmacology*; D023083:beta-Defensins / Q000494:pharmacology*
chemical_list: D016207:Cytokines; C106641:DEFB4A protein, human; D016328:NF-kappa B; D012333:RNA, Messenger; D023084:alpha-Defensins; D023083:beta-Defensins; C406413:human neutrophil peptide 1