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白细胞介素-1α诱导人中耳上皮细胞中β-防御素2上调需要Src依赖的Raf-MEK1/2-ERK信号通路的激活。

Activation of a Src-dependent Raf-MEK1/2-ERK signaling pathway is required for IL-1alpha-induced upregulation of beta-defensin 2 in human middle ear epithelial cells.

作者信息

Moon Sung-Kyun, Lee Haa-Yung, Li Jian-Dong, Nagura Mitsuyoshi, Kang Sung-Ho, Chun Young-Myoung, Linthicum Fred H, Ganz Tomas, Andalibi Ali, Lim David J

机构信息

Gonda Department of Cell and Molecular Biology, House Ear Institute, 2100 West 3rd Street, Los Angeles, CA 90057, USA.

出版信息

Biochim Biophys Acta. 2002 Jun 12;1590(1-3):41-51. doi: 10.1016/s0167-4889(02)00196-9.

DOI:10.1016/s0167-4889(02)00196-9
PMID:12063167
Abstract

beta-defensin 2 is produced by a variety of epithelial cell types in the body and exhibits potent antimicrobial activity against a variety of pathogens, including the bacteria that are most commonly associated with otitis media (OM). The human beta-defensin 2 (hBD-2) gene is an NF-kappa B regulated gene and a variety of proinflammatory stimuli can induce its expression. Although the presence of molecules of innate immunity such as lysozyme and lactoferrin has been demonstrated in the middle ear, to date there have been no reports on the expression of beta-defensin 2. In the present study, we demonstrate that beta-defensin 2 is expressed in the middle ear mucosa of humans and rats. We also show that it is expressed in a human middle ear epithelial cell line and that its expression is induced by proinflammatory stimuli such as interleukin 1 alpha (IL-1 alpha), tumor necrosis factor alpha (TNF-alpha), and lipopolysaccharide (LPS). Moreover, we demonstrate that the transcriptional activation of hBD-2 gene by IL-1 alpha is mediated through an Src-dependent Raf-MEK1/2-ERK signaling pathway.

摘要

β-防御素2由体内多种上皮细胞类型产生,对多种病原体具有强大的抗菌活性,包括与中耳炎(OM)最常相关的细菌。人β-防御素2(hBD-2)基因是一种受核因子κB调控的基因,多种促炎刺激可诱导其表达。尽管在中耳已证实存在溶菌酶和乳铁蛋白等先天免疫分子,但迄今为止尚无关于β-防御素2表达的报道。在本研究中,我们证明β-防御素2在人和大鼠的中耳黏膜中表达。我们还表明它在人中耳上皮细胞系中表达,并且其表达由白细胞介素1α(IL-1α)、肿瘤坏死因子α(TNF-α)和脂多糖(LPS)等促炎刺激诱导。此外,我们证明IL-1α对hBD-2基因的转录激活是通过Src依赖的Raf-MEK1/2-ERK信号通路介导的。

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