SOLUBLE IL-1 RECEPTOR-TYPE-I BINDS TO HUMAN DERMAL FIBROBLASTS AND INDUCES CALCIUM FLUX

Soluble cytokine receptors appear to modify ligand concentrations by s tabilizing ligands or by specifically inhibiting interactions of ligan ds with their membrane-bound receptors, Here we describe a new functio n of the soluble interleukin-1 receptor type I (IL-1sR I). This recept or induced a transient rise of intracellular free calcium concentratio n in human dermal fibroblasts in a dose-dependent fashion. Mobilizatio n of calcium by IL-1sR I was abolished in the presence of an equimolar concentration of IL-1 receptor antagonist (IL-1ra), Neutralizing anti bodies against IL-1 beta also abolished calcium mobilization stimulate d with IL-1sR I indicating that IL-1 beta is involved. IL-1sR I bound with high affinity (K-d 1-2 nM) to the fibroblasts. In addition, IL-1s R I enhanced expression of IL-6 and IL-8 mRNA. The observation that IL -1sR I can act as a ligand and agonist for membrane IL-1 extends the c oncept of the ligand-receptor functions of both IL-1 and IL-1sR I and adds a new dimension to the cytokine network. (C) 1998 Federation of E uropean Biochemical Societies.