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.
Bradford
P G
PG
Department of Pharmacology and Toxicology, State University of New York at Buffalo, Buffalo, New York, 14214-3000, USA. pgb@buffalo.edu
Maglich
J M
JM
Kirkwood
K L
KL
D016475:3T3 Cells; D000818:Animals; D015220:Calcium Channels / Q000235:genetics* / Q000378:metabolism; D002460:Cell Line; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D053496:Inositol 1,4,5-Trisphosphate Receptors; D007375:Interleukin-1 / Q000494:pharmacology*; D015850:Interleukin-6 / Q000378:metabolism*; D051379:Mice; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics* / Q000378:metabolism; D014407:Tumor Cells, Cultured
D015220:Calcium Channels; C506926:ITPR1 protein, human; D053496:Inositol 1,4,5-Trisphosphate Receptors; D007375:Interleukin-1; D015850:Interleukin-6; D018160:Receptors, Cytoplasmic and Nuclear