Soluble IL-1 receptor type I binds to human dermal fibroblasts and induces calcium flux.
Soluble cytokine receptors appear to modify ligand concentrations by stabilizing ligands or by specifically inhibiting interactions of ligands with their membrane-bound receptors. Here we describe a new function of the soluble interleukin-1 receptor type I (IL-1sR I). This receptor induced a transient rise of intracellular free calcium concentration in human dermal fibroblasts in a dose-dependent fashion. Mobilization of calcium by IL-1sR I was abolished in the presence of an equimolar concentration of IL-1 receptor antagonist (IL-1ra). Neutralizing antibodies against IL-1beta also abolished calcium mobilization stimulated with IL-1sR I indicating that IL-1beta is involved. IL-1sR I bound with high affinity (Kd 1-2 nM) to the fibroblasts. In addition, IL-1sR 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 concept of the ligand-receptor functions of both IL-1 and IL-1sR I and adds a new dimension to the cytokine network.
Spörri
B
B
Laboratory of Oral Cell Biology, Bern, Switzerland.
Wiesmann
U N
UN
Ochsenbein
R M
RM
Loetscher
M
M
Waelti
E R
ER
Lottaz
D
D
Bickel
M
M
D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics; D016209:Interleukin-8 / Q000235:genetics; D017136:Ion Transport; D011485:Protein Binding; D012333:RNA, Messenger / Q000235:genetics; D017472:Receptors, Interleukin-1 / Q000378:metabolism*; D012867:Skin / Q000166:cytology / Q000378:metabolism*; D015854:Up-Regulation
D007375:Interleukin-1; D015850:Interleukin-6; D016209:Interleukin-8; D012333:RNA, Messenger; D017472:Receptors, Interleukin-1; D002118:Calcium