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Immunogenetics

, Volume 51, Issue 4–5, pp 289–295 | Cite as

Role of nuclear factor-κ B in the expression by tumor necrosis factor-α of the human polymeric immunoglobulin receptor (pIgR ) gene

  • N. Takenouchi-Ohkubo
  • T. Takahashi
  • M. Tsuchiya
  • J. Mestecky
  • Z. Moldoveanu
  • I. Moro
ORIGINAL PAPER

Abstract

 We analyzed the mechanism of human polymeric immunoglobulin receptor (pIgR) gene upregulation by tumor necrosis factor (TNF)-α. Northern blot analysis showed that the expression of pIgR mRNA was enhanced by TNF-α stimulation. This activation was completely inhibited by RNA polymerase or protein synthesis inhibitors, suggesting that the regulation of pIgR gene expression depends on de novo RNA and protein synthesis. Furthermore, the stimulation of pIgR mRNA by TNF-α was decreased by pyrrolidinedithiocarbamate and l-1-4′-tosylamino-phenylethyl-chloromethyl ketone, which are known nuclear factor (NF)-κB inhibitors. For further analysis of gene regulation, we cloned and sequenced the 1.5-kb 5′-flanking region of the pIgR gene. In the upstream region, we found two NF-κB-binding motifs (named κB1 and κB2 from the 5′ region). An electrophoretic mobility shift assay indicated that two components of the NF-κB/Rel family, p50 and p65, bound with higher affinity to the κB2 element than to the κB1 element. We also analyzed pIgR gene expression using reporter plasmids expressing the firefly luciferase gene. Stimulation by TNF-α significantly activated the pIgR gene promoter, as a 775-bp upstream region of the pIgR gene increased luciferase gene expression in cells treated with TNF-α. The activation of promoter activity by TNF-α was abolished when a mutation was inserted into κB1 or κB2. These data indicated that pIgR gene expression induced by TNF-α is transcriptionally regulated via activation of NF-κB. In addition, there is a possibility that another factor may act in concert with NF-κB.

Key words Human Mucosa Gene regulation Cytokines Transcription factors 

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Copyright information

© Springer-Verlag Berlin Heidelberg 2000

Authors and Affiliations

  • N. Takenouchi-Ohkubo
    • 1
  • T. Takahashi
    • 1
  • M. Tsuchiya
    • 1
  • J. Mestecky
    • 2
  • Z. Moldoveanu
    • 2
  • I. Moro
    • 1
  1. 1.Department of Pathology, Nihon University School of Dentistry, Tokyo 101-8310, Japan e-mail: takenouchi@dent.nihon-u.ac.jp Tel.: +81-3-32198124 Fax: +81-3-32198340JP
  2. 2.Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL 35294, USAUS

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