Caspase-8- and JNK-dependent AP-1 activation is required for Fas ligand-induced IL-8 production

フォーマット:

論文

責任表示:

Matsumoto, Norihiko ; Imamura, Ryu ; Suda, Takashi

言語:

英語

出版情報:

Blackwell Publishing, 2007-03-01

著者名:

• Matsumoto, Norihiko
• Imamura, Ryu
• Suda, Takashi

掲載情報:

FEBS Journal

ISSN:

1742-464x      

巻:

279

通号:

9

開始ページ:

2376

終了ページ:

2384

バージョン:

author

概要:

Despite a dogma that apoptosis does not induce inflammation, Fas ligand (FasL), a well-known death factor, possesses pro-inflammatory activity. For example, FasL induces nuclear factor κB (NF-κB) activity and interleukin 8 (IL-8) production by engagement of Fas in human cells. Here, we found that a dominant negative mutant of c-Jun, a component of the activator protein-1 (AP-1) transcription factor, inhibits FasL-induced AP-1 activity and IL-8 production in … HEK293 cells. Selective inhibition of AP-1 did not affect NF-κB activation and vice versa, indicating that their activations were not sequential events. The FasL-induced AP-1 activation could be inhibited by deleting or introducing the lymphoproliferation (lpr)-type point mutation into the Fas death domain (DD), knocking down the Fas-associated DD protein (FADD), abrogating caspase-8 expression with small interfering RNAs, or using inhibitors for pan-caspase and caspase-8 but not caspase-1 or caspase-3. Furthermore, wildtype, but not a catalytically inactive mutant, of caspase-8 reconstituted the FasL-induced AP-1 activation in caspase-8-deficient cells. Fas ligand induced the phosphorylation of two of the three major mitogen-activated protein kinases (MAPKs): extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) but not p38 MAPK. Unexpectedly, an inhibitor for JNK but not for MAPK/ERK kinase inhibited the FasL-induced AP-1 activation and IL-8 production. These results demonstrate that FasL-induced AP-1 activation is required for optimal IL-8 production, and this process is mediated by FADD, caspase-8, and JNK. © 2007 The Authors. 続きを見る

URL:

http://hdl.handle.net/2297/6760