期刊
JOURNAL OF BIOLOGICAL CHEMISTRY
卷 289, 期 23, 页码 15942-15950出版社
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M114.557561
关键词
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资金
- Wellcome Trust
- Engineering and Physical Sciences Research Council (EPSRC)
- Biotechnology and Biological Sciences Research Council (BBSRC)
The cytokine interleukin-1 (IL-1) has two main pro-inflammatory forms, IL-1 alpha and IL-1 beta, which are central to host responses to infection and to damaging sterile inflammation. Processing of IL-1 precursor proteins to active cytokines commonly occurs through activation of proteases, notably caspases and calpains. These proteases are instrumental in cell death, and inflammation and cell death are closely associated, hence we sought to determine the impact of cell death pathways on IL-1 processing and release. Wediscovered that apoptotic regulation of caspase-8 specifically induced the processing and release of IL-1 beta. Conversely, necroptosis caused the processing and release of IL-1 alpha, and this was independent of IL-1 beta processing and release. These data suggest that the mechanism through which an IL-1-expressing cell dies dictates the nature of the inflammatory mechanism that follows. These insights may allow modification of inflammation through the selective targeting of cell death mechanisms during disease.
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