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Up-regulation of human β -defensin 2 by interleukin-1β in A549 cells: involvement of PI3K, PKC, p38 MAPK, JNK, and NF-κB

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Author(s)
장병철권택규백원기김상표서민호서성일
Alternative Author(s)
Jang, Byeong ChurlKwon, Taeg KyuBaek, Won KiKim, Sang PyoSuh, Min HoSuh, Seong Il
Publication Year
2004
Abstract
Induction of human β-defensin 2 (HBD-2) by interleukin-1β (IL-1β) in epithelial cells has been reported. However, the mechanism by which IL-1β up-regulates HBD-2 remains poorly understood. In this study, we investigated the effect of IL-1β on induction of HBD-2 in A549 cells. IL-1β markedly increased HBD-2 mRNA expression in concentration- and time-dependent manners. HBD-2 mRNA expression in response to IL-1β was attenuated by pretreatment of GF109203X, Go6976, and staurosporine [inhibitors of protein kinase C (PKC)], SB203580 [an inhibitor of p38 mitogen-activated protein kinase (MAPK)], SP600125 [an inhibitor of c-Jun N-terminal kinase (JNK)], and LY294002 [an inhibitor of phosphatidylinositol-3-kinase (PI3K)], but not PD98059 [an inhibitor of extracellular signal-regulated kinase (ERK)], suggesting involvement of PKC, p38 MAPK, JNK, and PI3K in this response. Interestingly, IL-1β induced nuclear factor-κB (NF-κB) activation in A549 cells, which was shown by increased nuclear translocation of p65 NF-κB and degradation of IκB-α. Importantly, IL-1β-induced HBD-2 mRNA expression was inhibited by blockage of NF-κB activation using NF-κB inhibitors, including pyrrolidine dithiocarbamate and MG132. Specifically, IL-1β-induced nuclear translocation of NF-κB was in part attenuated by LY294002, but not by GF109203X, SB203580, and SP600125, suggesting PI3K-dependent nuclear translocation of NF-κB in response to IL-1β. Together, these results suggest that IL-1β induces HBD-2 mRNA expression in A549 cells, and the induction seems to be at least in part mediated through activation of NF-κB transcription factor as well as activation of signaling proteins of PKC, p38 MAPK, JNK, and PI3K, but not ERK.

Keywords
IL-1β;
Human β-defensin 2;
PKC;
MAPKs;
PI3K;
NF-κB
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