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

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

Research output: Contribution to journalArticle

69 Scopus citations

Abstract

β-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 β-defensin 2 (hBD-2) gene is an NF-κB 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 β-defensin 2. In the present study, we demonstrate that β-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 α), tumor necrosis factor alpha (TNF-α), and lipopolysaccharide (LPS). Moreover, we demonstrate that the transcriptional activation of hBD-2 gene by IL-1 α is mediated through an Src-dependent Raf-MEK1/2-ERK signaling pathway.

Original languageEnglish (US)
Pages (from-to)41-51
Number of pages11
JournalBiochimica et Biophysica Acta - Molecular Cell Research
Volume1590
Issue number1-3
DOIs
StatePublished - Jun 12 2002

Keywords

  • Middle ear epithelial cell
  • Src-dependent
  • β-defensin 2

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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