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.
Skip Nav Destination
Article navigation
1 August 1996
Article|
August 01 1996
Functional role of interleukin 1 beta (IL-1 beta) in IL-1 beta-converting enzyme-mediated apoptosis.
R M Friedlander,
R M Friedlander
Cardiovascular Research Center, Massachusetts General Hospital-East, Charlestown 02129, USA.
Search for other works by this author on:
V Gagliardini,
V Gagliardini
Cardiovascular Research Center, Massachusetts General Hospital-East, Charlestown 02129, USA.
Search for other works by this author on:
R J Rotello,
R J Rotello
Cardiovascular Research Center, Massachusetts General Hospital-East, Charlestown 02129, USA.
Search for other works by this author on:
J Yuan
J Yuan
Cardiovascular Research Center, Massachusetts General Hospital-East, Charlestown 02129, USA.
Search for other works by this author on:
R M Friedlander
Cardiovascular Research Center, Massachusetts General Hospital-East, Charlestown 02129, USA.
V Gagliardini
Cardiovascular Research Center, Massachusetts General Hospital-East, Charlestown 02129, USA.
R J Rotello
Cardiovascular Research Center, Massachusetts General Hospital-East, Charlestown 02129, USA.
J Yuan
Cardiovascular Research Center, Massachusetts General Hospital-East, Charlestown 02129, USA.
Online ISSN: 1540-9538
Print ISSN: 0022-1007
J Exp Med (1996) 184 (2): 717–724.
Citation
R M Friedlander, V Gagliardini, R J Rotello, J Yuan; Functional role of interleukin 1 beta (IL-1 beta) in IL-1 beta-converting enzyme-mediated apoptosis.. J Exp Med 1 August 1996; 184 (2): 717–724. doi: https://doi.org/10.1084/jem.184.2.717
Download citation file:
Sign in
Don't already have an account? Register
Client Account
You could not be signed in. Please check your email address / username and password and try again.
Could not validate captcha. Please try again.
Sign in via your Institution
Sign in via your InstitutionSuggested Content
Email alerts
Advertisement