Abstract
Interleukin-1 (IL-1) is known to be a potent stimulator of bone resorption. The effect of IL-1 has been shown to be mediated, at least in part, by IL-1-induced prostaglandin (PG) E2 production in osteoblasts. The intracellular signal transduction mechanism of IL-1 in the PG production, however, is unknown. In the present study using a mouse osteoblastic cell line, MC3T3-E1 (MC), the possible involvement of two representative signal transduction pathways, protein kinase A (PKA) or protein kinase C (PKC)-dependent pathway in the IL-1 alpha stimulated PGE2 production, was investigated. MC produced PGE2 30 min after the IL-1 stimulation. This was inhibited with cycloheximide, suggesting the involvement of de novo protein synthesis. The IL-1-induced PGE2 production was inhibited by H-7 in a dose dependent manner. Since H-7 is known to inhibit PKA as well as PKC, a more specific inhibitor of PKA KT5720 or staurosporin was used to determine the respective role of PKA or PKC in the production of PGE2. KT5720 inhibited the IL-1-induced PGE2 production in MC in a dose dependent fashion. Similarly, staurosporin inhibited the IL-1-induced PGE2 production in MC in a dose dependent manner. The effect of the activity of PKA or PKC on the production of PGE2 was also investigated. A stimulator of PKA, 8-bromoadenosine 3'5'-cyclicmonophosphate (8-Br-cAMP), as well as a stimulator of PKC phorbol 12-myristate 13-acetate (PMA) induced PGE2 production in MC. The effect of these agents on the PGE2 production was additive.(ABSTRACT TRUNCATED AT 250 WORDS)
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