title: Caspase 3 inactivates biologically active full length interleukin-33 as a classical cytokine but does not prohibit nuclear translocation.
abstract: IL-33 is a member of the IL-1 family of cytokines with dual function which either activates cells via the IL-33 receptor in a paracrine fashion or translocates to the nucleus to regulate gene transcription in an intracrine manner. We show that full length murine IL-33 is active as a cytokine and that it is not processed by caspase 1 to mature IL-33 but instead cleaved by caspase 3 at aa175 to yield two products which are both unable to bind to the IL-33 receptor. Full length IL-33 and its N-terminal caspase 3 breakdown product, however, translocate to the nucleus. Finally, bioactive IL-33 is not released by cells constitutively or after activation. This suggests that IL-33 is not a classical cytokine but exerts its function in the nucleus of intact cells and only activates others cells via its receptor as an alarm mediator after destruction of the producing cell.
authors.affiliation: Immunology FB 08, Justus-Liebig-University, Winchesterstrasse 2, 35394 Giessen, Germany.
authors.forename: Shafaqat
authors.initials: S
authors.lastname: Ali
authors.forename: Dang Quan
authors.initials: DQ
authors.lastname: Nguyen
authors.forename: Werner
authors.initials: W
authors.lastname: Falk
authors.forename: Michael Uwe
authors.initials: MU
authors.lastname: Martin
mesh_terms: D021581:Active Transport, Cell Nucleus; D000818:Animals; D053148:Caspase 3 / Q000378:metabolism*; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism*; D006801:Humans; D000067596:Interleukin-33; D007378:Interleukins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: C506536:IL33 protein, human; D000067596:Interleukin-33; D007378:Interleukins; D009687:Nuclear Proteins; D053148:Caspase 3