Pre-interleukin-1α expression reduces cell growth and increases interleukin-6 production in SaOS-2 osteosarcoma cells: Differential inhibitory effect of interleukin-1 receptor antagonist (icIL-1Ra1)

• Published in: Cytokine (Philadelphia, Pa.) Pa.), 2005-07, Vol.31 (2), p.153-160
• Main Authors: Palmer, Gaby, Trolliet, Stéphanie, Talabot-Ayer, Dominique, Mézin, Françoise, Magne, David, Gabay, Cem
• Format: Article
• Language: English
• Subjects: Cell growth; Interleukin-1; Interleukin-1 receptor antagonist; Osteosarcoma; Proliferation
• ISSN: 1043-4666; 1096-0023
• DOI: 10.1016/j.cyto.2005.03.007

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-1α precursor (preIL-1α) led to the hypothesis that icIL-1Ra variants might antagonize the intracellular actions of preIL-1α. The aim of this study was to investigate effects of preIL-1α and icIL-1Ra1 in stably transfected SaOS-2 cells. Expression of preIL-1α 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-1α. In contrast, the production of IL-6 induced by preIL-1α was decreased in icIL-1Ra1 co-transfected cells. In conclusion, expression of preIL-1α 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-1α are not necessarily susceptible to inhibition by icIL-1Ra1.