title: Contradictory functions (activation/termination) of neutrophil proteinase 3 enzyme (PR3) in interleukin-33 biological activity.
abstract: IL-1 family ligand does not possess a typical hydrophobic signal peptide and needs a processing enzyme for maturation. The maturation process of IL-33 (IL-1F11), a new member of the IL-1 family ligand, remains unclear. Precursor IL-33 ligand affinity column isolates neutrophil proteinase 3 (PR3) from human urinary proteins. PR3 is a known IL-1 family ligand-processing enzyme for IL-1β (IL-1F2) and IL-18 (IL-1F4), including other inflammatory cytokines. We investigated PR3 in the maturation process of precursor IL-33 because we isolated urinary PR3 by using the precursor IL-33 ligand affinity column. PR3 converted inactive human and mouse precursor IL-33 proteins to biological active forms; however, the increase of PR3 incubation time abrogated IL-33 activities. Unlike caspase-1-cleaved precursor IL-18, PR3 cut precursor IL-33 and IL-18 at various sites and yielded multibands. The increased incubation period of PR3 abated mature IL-33 in a time-dependent manner. The result is consistent with the decreased bioactivity of IL-33 along with the increased PR3 incubation time. Six different human and mouse recombinant IL-33 proteins were expressed by the predicted consensus amino acid sequence of PR3 cleavage sites and tested for bioactivities. The human IL-33/p1 was highly active, but human IL-33/p2 and p3 proteins were inactive. Our results suggest the dual functions (activation/termination) of PR3 in IL-33 biological activity.
authors.affiliation: Laboratory of Cytokine Immunology, Department of Biomedical Science and Technology, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul 143-701, Korea.
authors.forename: Suyoung
authors.initials: S
authors.lastname: Bae
authors.forename: Taebong
authors.initials: T
authors.lastname: Kang
authors.forename: Jaewoo
authors.initials: J
authors.lastname: Hong
authors.forename: Siyoung
authors.initials: S
authors.lastname: Lee
authors.forename: Jida
authors.initials: J
authors.lastname: Choi
authors.forename: Hyunjhung
authors.initials: H
authors.lastname: Jhun
authors.forename: Areum
authors.initials: A
authors.lastname: Kwak
authors.forename: Kwangwon
authors.initials: K
authors.lastname: Hong
authors.forename: Eunsom
authors.initials: E
authors.lastname: Kim
authors.forename: Seunghyun
authors.initials: S
authors.lastname: Jo
authors.forename: Soohyun
authors.initials: S
authors.lastname: Kim
mesh_terms: D000818:Animals; D020170:Caspase 1 / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D006801:Humans; D020382:Interleukin-18 / Q000235:genetics / Q000378:metabolism; D000067596:Interleukin-33; D007378:Interleukins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D053146:Myeloblastin / Q000235:genetics / Q000378:metabolism*; D011498:Protein Precursors / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: C506536:IL33 protein, human; C506535:Il33 protein, mouse; D020382:Interleukin-18; D000067596:Interleukin-33; D007378:Interleukins; D011498:Protein Precursors; D011994:Recombinant Proteins; D053146:Myeloblastin; D020170:Caspase 1