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Am J Physiol Lung Cell Mol Physiol 288: L508-L513, 2005. First published November 19, 2004; doi:10.1152/ajplung.00076.2004
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Differential effects of {alpha}- and {beta}-defensin on cytokine production by cultured human bronchial epithelial cells

Noriho Sakamoto,1 Hiroshi Mukae,1 Takeshi Fujii,1 Hiroshi Ishii,1 Sumako Yoshioka,1 Tomoyuki Kakugawa,1 Kanako Sugiyama,1 Yohei Mizuta,1 Jun-ichi Kadota,2 Masamitsu Nakazato,3 and Shigeru Kohno1

1Second Department of Internal Medicine, Nagasaki University School of Medicine, Nagasaki, Japan; 2Second Department of Internal Medicine, Oita University Faculty of Medicine, Oita, Japan; and 3Third Department of Internal Medicine, Miyazaki Medical College, Miyazaki, Japan

Submitted 5 March 2004 ; accepted in final form 15 November 2004

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-1{beta} mRNA expression in a dose-dependent manner and also enhanced IL-8 protein secretion and NF-{kappa}B DNA binding activity. The 24-h treatments with >20 µg/ml of HNP-1 or >50 µg/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.

human neutrophil peptide-1; human {beta}-defensin-2; interleukin-8; nuclear factor-{kappa}B; cytotoxicity


Address for reprint requests and other correspondence: H. Mukae, Second Dept. of Internal Medicine, Nagasaki Univ. School of Medicine, Sakamoto 1-7-1, Nagasaki 852-8501, Japan (E-mail: hmukae{at}net.nagasaki-u.ac.jp)




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