Up-regulation of human β-defensin 2 by interieukin-1β in A549 cells:: involvement of PI3K, PKC, p38 MAPK, JNK, and NF-κB
Up-regulation of human β-defensin 2 by interieukin-1β in A549 cells:: involvement of PI3K, PKC, p38 MAPK, JNK, and NF-κB
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DOI：
10.1016/j.bbrc.2004.06.049
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发表时间：
2004-07-30
影响因子：
3.1
通讯作者：
Suh, SI
中科院分区：
文献类型：
--
作者：
Jang, BC;Lim, KJ;Suh, SI
已报道了白细胞介素-1 β（IL-1 β）在上皮细胞中诱导人β-防御素2（HBD-2）。然而，IL-1 β上调HBD-2的机制仍然知之甚少。在这项研究中，我们研究了IL-1 β对A549细胞中HBD-2诱导的影响。IL-1 β以浓度和时间依赖性方式显著增加HBD-2 mRNA表达。IL-1 β诱导的HBD-2 mRNA表达可通过GF 109203 X、Go 6976、staurosporine [蛋白激酶C（PKC）抑制剂]、SB 203580 [p38丝裂原活化蛋白激酶（MAPK）抑制剂]、SP 600125 [c-Jun N-末端激酶（JNK）抑制剂]、和LY 294002 [磷脂酰肌醇-3-激酶（PI 3 K）的抑制剂]，而不是PD 98059 [细胞外信号调节激酶（ERK）的抑制剂]，表明PKC、p38 MAPK、JNK和PI 3 K参与了这种反应。有趣的是，IL-1 β可诱导A549细胞核因子-κ B（NF-κ B）活化，表现为p65 NF-κ B核转位增加和IkappaB-α降解。重要的是，IL-1 β诱导的HBD-2 mRNA表达通过使用NF-κ B抑制剂（包括吡咯烷二硫代氨基甲酸酯和MG 132）阻断NF-κ B活化而受到抑制。具体而言，IL-1 β诱导的NF-κ B核转位被LY 294002部分减弱，但不被GF 109203 X、SB 203580和SP 600125减弱，这表明NF-κ B核转位响应于IL-1 β而依赖于PI 3 K。总之，这些结果表明，IL-1 β诱导A549细胞中HBD-2 mRNA的表达，并且该诱导似乎至少部分地通过激活NF-κ B转录因子以及激活PKC、p38 MAPK、JNK和PI 3 K信号蛋白介导，而不是ERK。(C)2004年爱思唯尔公司All rights reserved.
Induction of human beta-defensin 2 (HBD-2) by interleukin-1beta (IL-1beta) in epithelial cells has been reported. However, the mechanism by which IL-1beta up-regulates HBD-2 remains poorly understood. In this study, we investigated the effect of IL-1beta on induction of HBD-2 in A549 cells. IL-1beta markedly increased HBD-2 mRNA expression in concentration- and time-dependent manners. HBD-2 mRNA expression in response to IL-1beta 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-1beta induced nuclear factor-kappaB (NF-kappaB) activation in A549 cells, which was shown by increased nuclear translocation of p65 NF-kappaB and degradation of IkappaB-alpha. Importantly, IL-1beta-induced HBD-2 mRNA expression was inhibited by blockage of NF-kappaB activation using NF-kappaB inhibitors, including pyrrolidine dithiocarbamate and MG132. Specifically, IL-1beta-induced nuclear translocation of NF-kappaB was in part attenuated by LY294002, but not by GF109203X, SB203580, and SP600125, suggesting PI3K-dependent nuclear translocation of NF-kappaB in response to IL-1beta. Together, these results suggest that IL-1beta induces HBD-2 mRNA expression in A549 cells, and the induction seems to be at least in part mediated through activation of NF-kappaB transcription factor as well as activation of signaling proteins of PKC, p38 MAPK, JNK, and PI3K, but not ERK. (C) 2004 Elsevier Inc. All rights reserved.