title: Pre-interleukin-1alpha expression reduces cell growth and increases interleukin-6 production in SaOS-2 osteosarcoma cells: Differential inhibitory effect of interleukin-1 receptor antagonist (icIL-1Ra1).
abstract: Interleukin-1 receptor antagonist (IL-1Ra) inhibits the classical biological effects of interleukin (IL)-1 by preventing its binding to IL-1 receptors. There are, however, four different isoforms of IL-1Ra, of which three are intracellular (icIL-1Ra1, 2, 3). Due to their localization, icIL-1Ras cannot interact with cell surface IL-1 receptors and have been suggested to carry out specific functions inside cells. The recent description of nuclear effects of the IL-1alpha precursor (preIL-1alpha) led to the hypothesis that icIL-1Ra variants might antagonize the intracellular actions of preIL-1alpha. The aim of this study was to investigate effects of preIL-1alpha and icIL-1Ra1 in stably transfected SaOS-2 cells. Expression of preIL-1alpha significantly decreased cell growth and this effect was not reversed by addition of exogenous IL-1Ra, suggesting an intracellular mode of action. Transfection of SaOS-2 cells with icIL-1Ra1 did not affect their growth. Furthermore, co-expression of icIL-1Ra1 did not reverse the growth inhibitory effect of preIL-1alpha. In contrast, the production of IL-6 induced by preIL-1alpha was decreased in icIL-1Ra1 co-transfected cells. In conclusion, expression of preIL-1alpha decreased the growth of SaOS-2 cells, likely by an intracellular mechanism. Co-expression of icIL-1Ra1 did not antagonize this effect, indicating that intracellular effects of preIL-1alpha are not necessarily susceptible to inhibition by icIL-1Ra1.
authors.affiliation: Division of Rheumatology, University Hospital, Geneva, Switzerland; Department of Pathology and Immunology, University of Geneva School of Medicine, Geneva, Switzerland.
authors.forename: Gaby
authors.initials: G
authors.lastname: Palmer
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Trolliet
authors.forename: Dominique
authors.initials: D
authors.lastname: Talabot-Ayer
authors.forename: Françoise
authors.initials: F
authors.lastname: Mézin
authors.forename: David
authors.initials: D
authors.lastname: Magne
authors.forename: Cem
authors.initials: C
authors.lastname: Gabay
mesh_terms: D002455:Cell Division / Q000502:physiology*; D045744:Cell Line, Tumor; D004797:Enzyme-Linked Immunosorbent Assay; D005455:Fluorescent Antibody Technique; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000378:metabolism*; D015850:Interleukin-6 / Q000096:biosynthesis*; D012516:Osteosarcoma / Q000378:metabolism* / Q000473:pathology; D010957:Plasmids; D011498:Protein Precursors / Q000378:metabolism*; D012795:Sialoglycoproteins / Q000502:physiology*; D014162:Transfection
chemical_list: C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D015850:Interleukin-6; D011498:Protein Precursors; D012795:Sialoglycoproteins; C043830:interleukin 1 precursor