Functional role of interleukin 1 beta (IL-1 beta) in IL-1 beta-converting enzyme-mediated apoptosis.
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- R M Friedlander
- Cardiovascular Research Center, Massachusetts General Hospital-East, Charlestown 02129, USA.
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- V Gagliardini
- Cardiovascular Research Center, Massachusetts General Hospital-East, Charlestown 02129, USA.
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- R J Rotello
- Cardiovascular Research Center, Massachusetts General Hospital-East, Charlestown 02129, USA.
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- J Yuan
- Cardiovascular Research Center, Massachusetts General Hospital-East, Charlestown 02129, USA.
抄録
<jats:p>Prointerleukin-1 beta (pro-IL-1 beta) is the only known physiologic substrate of the interleukin-1 beta (IL-1 beta)-converting enzyme (ICE), the founding member of the ICE/ced-3 cell death gene family. Since secreted mature IL-1 beta has been detected after apoptosis, we investigated whether this cytokine, when produced endogenously, plays a role in cell death. We found that hypoxia-induced apoptosis can be inhibited by either the IL-1 receptor antagonist (IL-1Ra) or by neutralizing antibodies to IL-1 or to its type 1 receptor. IL-1Ra also inhibits apoptosis induced by trophic factor deprivation in primary neurons, as well as by tumor necrosis factor alpha in fibroblasts. In addition, during the G1/S phase arrest, mature IL-1 beta induces apoptosis through a pathway independent of CrmA-sensitive gene activity. We also demonstrate that Ice, when expressed in COS cells, requires the coexpression of pro-IL-1 beta for the induction of apoptosis, which is inhibited by IL-1Ra. Interestingly, we found that mature IL-1 beta has antiapoptotic activity when added exogenously before the onset of hypoxia, which we found is caused in part by its ability to downregulate the IL-1 receptor. Our findings demonstrate that pro-IL-1 beta is a substrate of ICE relevant to cell death, and depending on the temporal cellular commitment to apoptosis, mature IL-1 beta may function as a positive or negative mediator of cell death.</jats:p>
収録刊行物
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- The Journal of experimental medicine
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The Journal of experimental medicine 184 (2), 717-724, 1996-08-01
Rockefeller University Press
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詳細情報 詳細情報について
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- CRID
- 1363107370310389248
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- NII論文ID
- 30017431376
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- ISSN
- 15409538
- 00221007
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