C/EBP Homologous Protein (CHOP) Is Crucial for the Induction of Caspase-11 and the Pathogenesis of Lipopolysaccharide-Induced Inflammatio
- 15 May 2006
- journal article
- Published by The American Association of Immunologists in The Journal of Immunology
- Vol. 176 (10), 6245-6253
- https://doi.org/10.4049/jimmunol.176.10.6245
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-1β 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-1β, 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.Keywords
This publication has 39 references indexed in Scilit:
- Activating Transcription Factor 4 Is Translationally Regulated by Hypoxic StressMolecular and Cellular Biology, 2004
- Endoplasmic reticulum stress response is involved in nonsteroidal anti-inflammatory drug-induced apoptosisCell Death & Differentiation, 2004
- hsp70-DnaJ chaperone pair prevents nitric oxide- and CHOP-induced apoptosis by inhibiting translocation of Bax to mitochondriaCell Death & Differentiation, 2004
- Ischemia-induced neuronal cell death is mediated by the endoplasmic reticulum stress pathway involving CHOPCell Death & Differentiation, 2004
- Caspase-11 Gene Expression in Response to Lipopolysaccharide and Interferon-γ Requires Nuclear Factor-κB and Signal Transducer and Activator of Transcription (STAT) 1Published by Elsevier BV ,2002
- IRE1 couples endoplasmic reticulum load to secretory capacity by processing the XBP-1 mRNANature, 2002
- XBP1 mRNA Is Induced by ATF6 and Spliced by IRE1 in Response to ER Stress to Produce a Highly Active Transcription FactorCell, 2001
- Identification of novel stress-induced genes downstream of chopThe EMBO Journal, 1998
- Induction of apoptosis in fibroblasts by IL-1β-converting enzyme, a mammalian homolog of the C. elegans cell death gene ced-3Cell, 1993
- A novel heterodimeric cysteine protease is required for interleukin-1βprocessing in monocytesNature, 1992