| First Author | Lüthi AU | Year | 2009 |
| Journal | Immunity | Volume | 31 |
| Issue | 1 | Pages | 84-98 |
| PubMed ID | 19559631 | Mgi Jnum | J:151673 |
| Mgi Id | MGI:4354713 | Doi | 10.1016/j.immuni.2009.05.007 |
| Citation | Luthi AU, et al. (2009) Suppression of interleukin-33 bioactivity through proteolysis by apoptotic caspases. Immunity 31(1):84-98 |
| abstractText | Interleukin-33 (IL-33) is a member of the IL-1 family and is involved in polarization of T cells toward a T helper 2 (Th2) cell phenotype. IL-33 is thought to be activated via caspase-1-dependent proteolysis, similar to the proinflammatory cytokines IL-1 beta and IL-18, but this remains unproven. Here we showed that IL-33 was processed by caspases activated during apoptosis (caspase-3 and -7) but was not a physiological substrate for caspases associated with inflammation (caspase-1, -4, and -5). Furthermore, caspase-dependent processing of IL-33 was not required for ST2 receptor binding or ST2-dependent activation of the NF-kappaB transcription factor. Indeed, caspase-dependent proteolysis of IL-33 dramatically attenuated IL-33 bioactivity in vitro and in vivo. These data suggest that IL-33 does not require proteolysis for activation, but rather, that IL-33 bioactivity is diminished through caspase-dependent proteolysis within apoptotic cells. Thus, caspase-mediated proteolysis acts as a switch to dampen the proinflammatory properties of IL-33. |
