IL-1β increases type 1 inositol trisphosphate receptor expression and IL-6 secretory capacity in osteoblastic cell cultures

Acute IL-6 secretion from osteosarcoma cells induced by the PI-linked hormones PTH(1-34) and endothelin-1 is potentiated by IL-1β. The present findings indicate that this potentiation is accompanied by increased signal transduction capacity. Specifically, IL-1β (30 pM) increased the B(max) of InsP₃ receptor binding (2.7-fold) and immunoblot showed a 2.4-fold increase specifically in the type 1 InsP₃ receptor protein. Northern analyses of IL- 1β-treated G-292 cells showed an 1.8-fold increase in type 1 InsP₃ receptor mRNA and, in IL-1β-treated murine MC3T3-E1 osteoblastic cells, an 8.4-fold enhancement of the type 1 InsP₃ receptor gene transcription. Promoter reporter assays confirmed the mRNA measurements and showed the effect of IL- 1β to be mediated by the major transcriptional regulatory region of the type 1 InsP₃ receptor promoter. The findings support the hypothesis that chronic regulators of osteoblast function, such as IL-1β, affect the capacity of cellular signal transduction through changes in InsP₃ receptor levels. (C) 2000 Academic Press.