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図 NF-κB活性化の古典的経路
Nuclear factor-κB(NF-κB)は,5種類のサブタイプからなるRel/ NF-κBファミリーの総称であり,非炎症病態ではI-κB(inhibitory κB)と結合し,核内移行が阻止され,細胞質内に存在する。敗血症などの全身性炎症病態では,Toll-like受容体,IL-1受容体,TNF受容体などの炎症性受容体の各リガンドとの反応により,IRAK(Interleukin-1 receptor-associated kinase),TRAF(tumor necrosis factor receptor –associated factor),TAK1(TGF-βactivated kinase 1)などのリン酸化酵素が活性化し,さらに細胞質内でIKK(inhibitory κB kinase)が活性化される。これにより,IKKのターゲット分子であるI-κBがリン酸化されると,I-κBは細胞質内でマルチユビキチン化を受け,細胞質内消化を受け,ペッドキャップ構造のとれた2量体NF-κBが核内へ移行し,DNA上のκB領域と結合することで炎症性分子の転写が高まる。NF-κBデコイ核酸を用いた遺伝子治療は,2量体NF-κBを補綴する2本鎖オリゴヌクレオチドとして作用し,細胞質内でDNA上のκB領域と競合し,NF-κB活性化を抑制する。