FACTORS INFLUENCING THE EFFECT OF THE SOLUBLE IL-6 RECEPTOR ON IL-6 RESPONSES IN HepG2 HEPATOCYTES

• Published in: Cytokine (Philadelphia, Pa.) Vol. 12; no. 6; pp. 774 - 779
• Main Authors: Paysant, Jerome, Blanqué, Roland, Vasse, Marc, Soria, Claudine, Soria, Jeannette, Gardner, Colin R
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01-06-2000
• Subjects: Carcinoma, Hepatocellular; Cell Membrane - immunology; Dexamethasone - pharmacology; dexamethasone/fibrinogen/HepG2 hepatocytes/soluble IL-6 receptor; Gene Expression Regulation - drug effects; Gene Expression Regulation - immunology; Humans; Interleukin-6 - genetics; Interleukin-6 - pharmacology; Liver Neoplasms; Receptors, Interleukin-6 - genetics; Receptors, Interleukin-6 - physiology; Signal Transduction; Tumor Cells, Cultured; dexamethasone/fibrinogen/HepG2 hepatocytes/soluble IL-6 receptor
• ISSN: 1043-4666; 1096-0023
• DOI: 10.1006/cyto.1999.0649

The soluble IL-6 receptor (sIL-6R) can increase IL-6-induced signalling by forming a complex with IL-6 and membrane-bound gp130 (the receptor beta chain which transduces signals). The conditions affecting this response to sIL-6R were studied using fibrinogen release from HepG2 hepatocytes. Exogenous sIL-6R had no effect alone or in the presence of a submaximal concentration of IL-6, but increased responses to supramaximal IL-6 concentrations in a concentration-related manner. Dexamethasone increased the expression of the membrane IL-6R and endogenous sIL6R release, and increased responses to supramaximal but not submaximal IL-6 concentrations. The amount of endogenous sIL-6R released is relatively small and is unlikely to influence the effects of the exogenous sIL-6R. The observed concentration-related decrease in sIL-6R production in the presence of IL-6 may indicate internalization of ligand/receptor complexes. This would significantly decrease the amount of IL-6R (soluble or membrane) available for signalling and limit continued functional response later in the cultures. These data indicate that the major factor influencing responses to exogenous sIL-6R is an excess of IL-6 which is necessary to form complexes with the sIL-6R, which can then interact with gp130 to increase signalling.