TGF-β Decreases the Stability of IL-18-Induced IFN-γ mRNA through the Expression of TGF-β-Induced Tristetraprolin in KG-1 Cells

• Inoue Yasumichi

  Department of Drug Metabolism and Disposition, Graduate School of Pharmaceutical Sciences, Nagoya City University

• Abe Kenji

  Department of Molecular Health Sciences, Graduate School of Pharmaceutical Sciences, Nagoya City University

• Onozaki Kikuo

  Department of Molecular Health Sciences, Graduate School of Pharmaceutical Sciences, Nagoya City University

• Hayashi Hidetoshi

  Department of Drug Metabolism and Disposition, Graduate School of Pharmaceutical Sciences, Nagoya City University

抄録

We have previously reported that transforming growth factor-β (TGF-β) down-regulates interferon-γ (IFN-γ) production in an interleukin-18 (IL-18) treated mouse natural killer (NK) cell line, LNK5E6. In LNK5E6 cells, TGF-β exhibited no inhibition of the IL-18-induced transcription of IFN-γ, but did stimulate the degradation of IFN-γ mRNA induced by IL-18. In the present study, we investigated the mechanism of the down-regulatory effects of TGF-β on IFN-γ mRNA expression in a human myelomonocytic cell line, KG-1, which produces IFN-γ in response to IL-18 alone. Interestingly, IL-18 induced the production of the IFN-γ through the stabilization of IFN-γ mRNA, but not the enhanced transcription of IFN-γ gene. The stability of IFN-γ mRNA was regulated by mRNA destabilizing elements in the 3′untranslated region (UTR) of IFN-γ mRNA, especially adenylate-uridylate (AU)-rich elements (AREs) in the 5′ half of 3′UTR. Tristetraprolin (TTP), one of the ARE-binding proteins, destabilizes IFN-γ mRNA, and IL-18 repressed the expression of TTP mRNA. Moreover, TGF-β repressed the IL-18-induced expression of IFN-γ mRNA through the induction of TTP mRNA to destabilize IFN-γ mRNA. Our data is the first to reveal that the crosstalk between IL-18 and TGF-β through the expression of TTP regulates the production of IFN-γ.

収録刊行物

• Ｂｉｏｌｏｇｉｃａｌ　＆　Ｐｈａｒｍａｃｅｕｔｉｃａｌ　Ｂｕｌｌｅｔｉｎ

  Ｂｉｏｌｏｇｉｃａｌ　＆　Ｐｈａｒｍａｃｅｕｔｉｃａｌ　Ｂｕｌｌｅｔｉｎ 38 (4), 536-544, 2015

  公益社団法人 日本薬学会

キーワード

• transforming growth factor-β (TGF-β)
• interleukin-18 (IL-18)
• interferon-γ (IFN-γ)
• tristetraprolin (TTP)

詳細情報

• CRID: 1390282679608483712
• NII論文ID: 130005062261
• NII書誌ID: AA10885497
• DOI: 10.1248/bpb.b14-00673
• ISSN: 13475215
• ISSN: 09186158
• NDL書誌ID: 026283551
• PubMed: 25832634
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I026283551
• Web Site: https://www.jstage.jst.go.jp/article/bpb/38/4/38_b14-00673/_pdf
• Web Site: https://search.jamas.or.jp/link/ui/2016001667
• 本文言語コード: en
• データソース種別:
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