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Am J Physiol Lung Cell Mol Physiol (November 19, 2004). doi:10.1152/ajplung.00076.2004
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Submitted on March 5, 2004
Accepted on November 15, 2004

Differential effects of alpha- and beta-defensin on cytokine production by cultured human bronchial epithelial cells

Noriho Sakamoto1, Hiroshi Mukae1*, Takeshi Fujii1, Hiroshi Ishii1, Sumako Yoshioka1, Tomoyuki Kakugawa1, Kanako Sugiyama1, Yohei Mizuta1, Jun-ichi Kadota2, Masamitsu Nakazato3, and Shigeru Kohno1

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

* To whom correspondence should be addressed. E-mail: hmukae{at}net.nagasaki-u.ac.jp.

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. Though {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 treatment 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.




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