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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.

Authors
Moon, SK; Lee, HY; Li, JD; Nagura, M; Kang, SH; Chun, YM; Linthicum, FH; Ganz, T; Andalibi, A; Lim, DJ
Citation
Biochimica et biophysica acta, 1590(1-3):41-51, 2002
Journal Title
Biochimica et biophysica acta
ISSN
0006-30021878-2434
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.
MeSH terms
AnimalsCells, CulturedEar, Middle/cytology/drug effects/*metabolismEpithelial Cells/drug effects/metabolismHumansImmunohistochemistryInterleukin-1/pharmacologyLipopolysaccharides/pharmacologyMAP Kinase Kinase 1MAP Kinase Kinase 2Mitogen-Activated Protein Kinase Kinases/*metabolismMitogen-Activated Protein Kinases/*metabolismModels, BiologicalMucous Membrane/drug effects/metabolismProtein-Serine-Threonine Kinases/*metabolismProtein-Tyrosine Kinases/*metabolismProto-Oncogene Proteins c-raf/*metabolismRNA, Messenger/genetics/metabolismRatsSignal TransductionTumor Necrosis Factor-alpha/pharmacologyUp-Regulation/drug effectsbeta-Defensins/*geneticssrc-Family Kinases/metabolism
PMID
12063167
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Journal Papers > School of Medicine / Graduate School of Medicine > Otolaryngology
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