title: Intracellular interleukin-1 receptor antagonist type 1 antagonizes the stimulatory effect of interleukin-1 alpha precursor on cell motility.
abstract: Interleukin (IL)-1alpha, a proinflammatory cytokine, is produced as a 33 kDa protein precursor (preIL-1alpha) which is cleaved to generate the 17 kDa C-terminal mature IL-1alpha (mIL-1alpha) and the 16kDa N-terminal IL-1alpha propiece (NIL-1alpha). The biological effect of IL-1alpha is regulated by the IL-1 receptor antagonist (IL-1Ra), its naturally occurring inhibitor. Four different isoforms of the IL-1Ra have been described, one secreted (sIL-1Ra) and three intracellular (icIL-1Ra1, 2, 3). Whether the icIL-1Ra1 isoform can antagonize some of the biological effects of intracellular IL-1alpha is still unknown. The aim of this study is to investigate effects of preIL-1alpha and icIL-1Ra1 on cell motility in stably transfected ECV304 cells. We show that expression of preIL-1alpha in ECV304 cells significantly increases cell motility. Furthermore, transfection with NIL-1alpha propiece also increases cell motility whereas this stimulatory effect was not observed by addition of exogenous mIL-1alpha, suggesting an intracellular effect of preIL-1alpha mediated by NIL-1alpha propiece. Co-transfection of ECV304 cells with icIL-1Ra1 completely antagonizes the stimulatory effect of preIL-1alpha and NIL-1alpha propiece on cell motility. In conclusion, NIL-1alpha propiece increases ECV304 cell motility and icIL-1Ra1 exerts intracellular functions regulating this stimulatory effect.
authors.affiliation: Division of Rheumatology, Department of Internal Medicine, University Hospital of Geneva, 26 avenue de Beau-séjour, 1211 Geneva 14, Switzerland.
authors.forename: Faten
authors.initials: F
authors.lastname: Merhi-Soussi
authors.forename: Marina
authors.initials: M
authors.lastname: Berti
authors.forename: Bernhard
authors.initials: B
authors.lastname: Wehrle-Haller
authors.forename: Cem
authors.initials: C
authors.lastname: Gabay
mesh_terms: D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology*; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000037:antagonists & inhibitors* / Q000502:physiology; D007424:Intracellular Fluid / Q000502:physiology*; D011498:Protein Precursors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors* / Q000502:physiology; D012795:Sialoglycoproteins / Q000502:physiology*; D014162:Transfection
chemical_list: C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D011498:Protein Precursors; D017472:Receptors, Interleukin-1; D012795:Sialoglycoproteins; C043830:interleukin 1 precursor