MISC

2000年5月

Transforming growth factor-β inhibits lipopolysaccharide-stimulated expression of inflammatory cytokines in mouse macrophages through downregulation of activation protein 1 and CD14 receptor expression

Infection and Immunity
  • Kenichi Imai
  • ,
  • Akira Takeshita
  • ,
  • Shigemasa Hanazawa

68
5
開始ページ
2418
終了ページ
2423
記述言語
英語
掲載種別
DOI
10.1128/IAI.68.5.2418-2423.2000

The septic shock that occurs in gram-negative infections is caused by a cascade of inflammatory cytokines. Several studies showed that transforming growth factor-β1 (TGF-β1) inhibits this septic shock through suppression of expression of the lipopolysaccharide (LPS)-induced inflammatory cytokines. In this study, we investigated whether TGF-β1 inhibition of LPS-induced expression of inflammatory cytokines in the septic shock results from downregulation of LPS-stimulated expression of CD14, an LPS receptor. TGF-β1 markedly inhibited LPS stimulation of CD14 mRNA and protein levels in mouse macrophages. LPS-stimulated expression of CD14 was dramatically inhibited by addition of antisense, but not sense, c-fos and c-jun oligonucleotides. Since TGF-β1 pretreatment inhibited LPS-stimulated expression of c-fos and c-jun genes and also the binding of nuclear proteins to the consensus sequence of the binding site for activation protein 1 (AP-1), a heterodimer of c-Fos and c-Jun, in the cells, TGF-β1 inhibition of CD14 expression may be a consequence of downregulation of AP-1. LPS-stimulated expression of interleukin-1β and tumor necrosis factor alpha genes in the cells was inhibited by addition of CD14 antisense oligonucleotide. Also, TGF-β1 inhibited the LPS-stimulated production of both inflammatory cytokines by the macrophages. In addition, TGF-β1 inhibited expression of the two cytokines in several organs of mice receiving LPS. Thus, our results suggest that TGF- β1 inhibition of LPS-stimulated inflammatory responses resulted from downregulation of CD14 and also may be a possible mechanism of TGF-β1 inhibition of LPS-induced septic shock.

リンク情報
DOI
https://doi.org/10.1128/IAI.68.5.2418-2423.2000
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/10768925

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