p70腫瘍死滅因子受容体は,細胞毒性を媒介する
1Institute of Cancer and Developmental Biology, Syntex Research, Palo Alto, California 94303.
Cell
|July 10, 1992
まとめ
腫瘍細胞を殺す腫瘍死滅因子 (TNF) は,p55およびp70受容体によって媒介されます. p70受容体は,特に腫瘍細胞死亡を媒介し,TNFを標的とするがん治療に対する新しい洞察を提供します.
科学分野:
- 免疫学 免疫学とは
- 細胞生物学 細胞生物学
- 分子生物学は分子生物学である.
背景:
- 腫瘍死滅因子アルファ (TNF) は選択的な腫瘍細胞細胞毒性を示すが,その背後にあるメカニズムは不明である.
- TNFの作用は2つの異なる細胞表面受容体:p55とp70によって媒介されます.
- TNFに対する腫瘍細胞の異なる感受性は,受容体特異的な役割を示唆する.
研究 の 目的:
- TNF誘発の細胞毒性におけるp70受容体の特定の役割を調査する.
- 様々な細胞タイプにおけるTNF効果を媒介するp55およびp70受容体の異なる機能を明らかにする.
主な方法:
- マウスTA1細胞,ヒトHeLa細胞,およびNIH 3T3マウス線維芽細胞を使用した.
- ヒト (h) とマウス (m) のTNF治療法を使用した.
- 機能分析のためにヒトp70受容体 (TNFR) を含む感染したHeLa細胞.
- TNF治療後の細胞活性およびc-fosおよびマンガン超酸化物ディスミュータゼ (MnSOD) の誘導を評価した.
主要な成果:
- マウスのTA1細胞はmTNFに敏感であるが,hTNFには敏感ではないが,p70受容体 (mTNFによって認識される) がその殺戮に関与していた.
- 主にp55を発現するHeLa細胞は,hTNFに抵抗性だったが,ヒトp70受容体との感染で細胞死を経験した.
- p70受容体を発現するHeLa細胞は,TNFによるc-fosとMnSOD誘導の減少を示した.
- mTNFに敏感なNIH 3T3線維芽細胞は,hTNFに敏感になり,人間のp70受容体を過剰に発現すると,mTNFの感受性が高まりました.
結論:
- p70受容体は,TNF誘発の細胞毒性において,直接的かつ重要な役割を果たします.
- p70受容体の異なる発現または機能は,様々な細胞タイプにおけるTNF感受性に寄与する.
- これらの発見は,TNFの選択的作用のメカニズム的基礎を提供し,p70受容体の治療的ターゲティングを示唆しています.
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