Factors influencing the effect of the soluble IL-6 receptor on IL-6 responses in HepG2 hepatocytes.
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.
Paysant
J
J
Laboratoire DIFEMA, Université de Rouen, France.
Blanqué
R
R
Vasse
M
M
Soria
C
C
Soria
J
J
Gardner
C R
CR
D006528:Carcinoma, Hepatocellular; D002462:Cell Membrane / Q000276:immunology; D003907:Dexamethasone / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics* / Q000494:pharmacology*; D008113:Liver Neoplasms; D019947:Receptors, Interleukin-6 / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction; D014407:Tumor Cells, Cultured
D015850:Interleukin-6; D019947:Receptors, Interleukin-6; D003907:Dexamethasone