IL-1 beta 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-1 beta. The present findings indicate that this potentiation is accompanied by increased signal transduction capacity. Specifically, IL-1 beta (30 pM) increased the B(max) of InsP(3) receptor binding (2. 7-fold) and immunoblot showed a 2.4-fold increase specifically in the type 1 InsP(3) receptor protein. Northern analyses of IL-1 beta-treated G-292 cells showed an 1.8-fold increase in type 1 InsP3 receptor mRNA and, in IL-1 beta-treated murine MC3T3-E1 osteoblastic cells, an 8.4-fold enhancement of the type 1 InsP(3) receptor gene transcription. Promoter reporter assays confirmed the mRNA measurements and showed the effect of IL-1 beta to be mediated by the major transcriptional regulatory region of the type 1 InsP(3) receptor promoter. The findings support the hypothesis that chronic regulators of osteoblast function, such as IL-1 beta, affect the capacity of cellular signal transduction through changes in InsP(3) receptor levels. Copyright 2000 Academic Press.