SB203580 enhances interleukin-1 receptor antagonist gene expression in IFN-γ-stimulated BV2 microglial cells through a composite nuclear factor-κB/PU.1 binding site

Jin Sun Park, Soo Hyun Jung, Hyemyung Seo, Hee Sun Kim

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Interleukin-1 receptor antagonist (IL-1ra) is a naturally occurring antagonist of IL-1α and IL-1β binding to the IL-1 receptors and alleviates various inflammatory reactions. Therefore, the upregulation of IL-1ra expression is important for preventing and/or treating inflammatory diseases including many neurodegenerative diseases. This study found that SB203580, which is generally known as a p38 MAP kinase inhibitor and an anti-inflammatory agent, increased the level of IL-1ra expression in IFN-γ-stimulated BV2 microglial cells. This effect is believed to occur through the inhibition of protein kinase B (PKB), independently of the p38 MAP kinase pathways. Further mechanistic studies using an IL-1ra promoter revealed that a composite NF-κB/PU.1 binding site plays an important role in this SB203580-mediated upregulation of IL-1ra. Considering that IFN-γ is a major stimulator of the innate and adaptive immune responses, the upregulation of anti-inflammatory IL-1ra expression by SB203580 in the IFN-γ-stimulated microglia might provide a new therapeutic modality for various inflammatory diseases of the central nervous system.

Original languageEnglish
Pages (from-to)169-174
Number of pages6
JournalNeuroscience Letters
Volume416
Issue number2
DOIs
StatePublished - 12 Apr 2007

Bibliographical note

Funding Information:
This work was supported by Korea Research Foundation Grant KRF-2004-015-C00469 to H.S. Kim. J.S. Park was supported by Brain Korea 21 grant in 2006.

Keywords

  • IFN-γ
  • IL-1 receptor antagonist
  • Microglia
  • NF-κB/PU.1
  • Protein kinase B
  • SB203580

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