title: C/EBP homologous protein (CHOP) is crucial for the induction of caspase-11 and the pathogenesis of lipopolysaccharide-induced inflammation.
abstract: C/EBP homologous protein (CHOP)/growth arrest and DNA damage-inducible gene 153 is a C/EBP family transcription factor which is involved in endoplasmic reticulum (ER) stress-mediated apoptosis. To determine whether the ER stress-CHOP pathway is involved in the pathogenesis of the lung inflammation, mice were given LPS intratracheally. Treatment with LPS induced mRNAs for CHOP and BiP. The LPS-induced inflammation in lung, including the IL-1beta activity in bronchoalveolar lavage fluid, was attenuated in the Chop knockout mice. Caspase-11, which is needed for the activation of procaspase-1 and pro-IL-1beta, was induced by LPS treatment in the lung and primary cultured macrophages. The induction of caspase-11 by LPS was suppressed in Chop knockout mice. Caspase-11 was also induced by such ER stress inducers as thapsigargin or tunicamycin. These results show that CHOP plays a crucial role in the pathogenesis of inflammation through the induction of caspase-11.
authors: Department of Molecular Genetics, Graduate School of Medical Sciences, Kumamoto University, Honjo 1-1-1, Kumamoto 860-8556, Japan.
authors: Motoyoshi
authors: M
authors: Endo
authors: Masataka
authors: M
authors: Mori
authors: Shizuo
authors: S
authors: Akira
authors: Tomomi
authors: T
authors: Gotoh