Apoptosis signal-regulating kinase 1 regulates the expression of caspase-11.
Caspase-11 is an inducible caspase involved in the regulation of cell death and inflammation. In the present study, we examined whether apoptosis signal-regulating kinase 1 (Ask1)-mediated signaling pathway is involved in the expression of caspase-11 induced by lipopolysaccharide (LPS). We found that the induction of caspase-11 was suppressed by the inhibitors of NADPH oxidase (Nox) or knockdown of Nox4 that acts downstream of toll-like receptor 4 and generates Ask1-activating reactive oxygen species. Overexpression of dominant negative tumor necrosis factor receptor associate factor 6 also suppressed the induction of caspase-11. Importantly, knockdown or dominant negative form of Ask1 suppressed the induction of caspase-11 following LPS stimulation. Taken together, our results show that Ask1 regulates the expression of caspase-11 following LPS stimulation.
Choi
Jong-Ryoul
JR
Department of Molecular Biology, Sejong University, Seoul 143-747, Republic of Korea.
Heo
Hyejung
H
Lang
Yoo
Y
Shin
Ki Soon
KS
Kang
Shin Jung
SJ
D000818:Animals; D020169:Caspases / Q000096:biosynthesis / Q000235:genetics*; D053471:Caspases, Initiator; D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000187:drug effects; D008070:Lipopolysaccharides / Q000494:pharmacology; D048848:MAP Kinase Kinase Kinase 5 / Q000502:physiology*; D051379:Mice; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D051197:Toll-Like Receptor 4
D008070:Lipopolysaccharides; D017382:Reactive Oxygen Species; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases; C422943:Nox4 protein, mouse; D048848:MAP Kinase Kinase Kinase 5; C101136:Casp4 protein, mouse; D020169:Caspases; D053471:Caspases, Initiator