Suppression of caspase-11 expression by histone deacetylase inhibitors.
It has been well documented that histone deacetylase inhibitors suppress inflammatory gene expression. Therefore, we investigated whether histone deacetylase inhibitors modulate the expression of caspase-11 that is known as an inducible caspase regulating both inflammation and apoptosis. In the present study, we show that sodium butyrate and trichostatin A, two structurally unrelated inhibitors of histone deacetylase (HDAC), effectively suppressed the induction of caspase-11 in mouse embryonic fibroblasts stimulated with lipopolysaccharides. Sodium butyrate inhibited the activation of upstream signaling events for the caspase-11 induction such as activation of p38 mitogen-activated protein kinase and c-Jun N-terminal kinase, degradation of inhibitor of kappaB, and activation of nuclear factor-kappaB. These results suggest that the HDAC inhibitor suppressed cytosolic signaling events for the induction of caspase-11 by inhibiting the deacetylation of non-histone proteins.
Heo
Hyejung
H
Department of Molecular Biology, Sejong University, 98 Gunja-dong, Gwangjin-gu, Seoul 143-747, Republic of Korea.
Yoo
Lang
L
Shin
Ki Soon
KS
Kang
Shin Jung
SJ
D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D000818:Animals; D002087:Butyrates / Q000494:pharmacology*; D061945:Caspase Inhibitors; D020169:Caspases / Q000096:biosynthesis*; D053471:Caspases, Initiator; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005347:Fibroblasts / Q000187:drug effects / Q000201:enzymology; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases / Q000378:metabolism; D006877:Hydroxamic Acids / Q000494:pharmacology*; D051550:I-kappa B Kinase; D048670:MAP Kinase Kinase 4 / Q000378:metabolism; D051379:Mice; D010766:Phosphorylation / Q000187:drug effects; D051996:Transcription Factor RelA / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D002087:Butyrates; D061945:Caspase Inhibitors; D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; C498144:Rela protein, mouse; D051996:Transcription Factor RelA; C012589:trichostatin A; D051550:I-kappa B Kinase; D048051:p38 Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; C101136:Casp4 protein, mouse; D020169:Caspases; D053471:Caspases, Initiator; D006655:Histone Deacetylases