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Functional Role of Interleukin 1ß (IL-1ß) in IL-1ß-converting Enzyme-mediated Apoptosis
Journal of Experimental Medicine
  • Robert M. Friedlander, Harvard University
  • Valeria Gagliardini, Harvard University
  • Rocco J. Rotello, Cedarville University
  • Junying Yuan, Massachusetts General Hospital
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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.
  • Apoptosis,
  • enzymes,
  • interleukin,
  • 1 beta
Citation Information
Robert M. Friedlander, Valeria Gagliardini, Rocco J. Rotello and Junying Yuan. "Functional Role of Interleukin 1ß (IL-1ß) in IL-1ß-converting Enzyme-mediated Apoptosis" Journal of Experimental Medicine Vol. 184 Iss. 2 (1996) p. 717 - 724
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