期刊
JOURNAL OF BIOLOGICAL CHEMISTRY
卷 280, 期 51, 页码 41827-41834出版社
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M510849200
关键词
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资金
- NIAMS NIH HHS [R01AR049217, R01AR048269] Funding Source: Medline
Macrophages play a pivotal role in the pathogenesis of a variety of diseases. These studies were performed to characterize the mechanisms by which Toll-like receptor 4 (TLR4)-mediated NF-kappa B activation promotes resistance to cell death in macrophages. When NF-kappa B activation was inhibited by a super-repressor, I kappa B alpha, the TLR4 ligand lipopolysaccharide induced the activation of caspase 8, the loss of mitochondrial transmembrane potential (Delta Psi(m)), and apoptotic cell death in macrophages. The inhibition of caspase 8 activation suppressed DNA fragmentation but failed to protect macrophages against the loss of Delta Psi(m) and resulted in necrotic cell death. In contrast, the reduction of receptor-interacting protein 1 suppressed the loss of Delta Psi(m) and inhibited apoptotic cell death. Further, when caspase 8 activation was suppressed, the knock down of receptor-interacting protein inhibited the loss of Delta Psi(m) and necrotic cell death. These observations demonstrate that following TLR4 ligation by lipopolysaccharide, NF-kappa B is a critical determinant of macrophage life or death, whereas caspase 8 determines the pathway employed.
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