Regulation of interleukin-6 production by prostaglandin E2 in fetal rat osteoblasts: role of protein kinase A signaling pathway

Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research
I MilletA Vignery

Abstract

Prostaglandin E2 (PGE2) is an abundant eicosanoid in bone that has been implicated in a number of pathological states associated with bone loss. Interleukin-6 (IL-6) is a cytokine that plays a critical role in bone remodeling and appears to act as a downstream effector of most bone-resorbing agents. In light of the evidence that PGE2 induces IL-6 in the bone environment, this study was designed to investigate whether PGE2 regulated IL-6 expression by osteoblasts. Here we demonstrate that PGE2 is a potent inducer of IL-6 production by fetal rat osteoblasts and synergizes with lipopolysaccharide to enhance IL-6. We show that PGE2 stimulates the activity of the IL-6 promoter in osteoblasts, suggesting that PGE2 controls IL-6 gene expression at least at the transcriptional level. Moreover, we show that PGE2-mediated IL-6 induction is prevented by the cAMP antagonist, Rp-cAMP, and the protein kinase A (PKA) inhibitors, KT5720 and H89. Thus, our data indicate that PGE2 involves the cAMP-PKA signaling pathway to regulate IL-6 gene expression in osteoblasts.

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Citations

Apr 25, 2000·Biochemical and Biophysical Research Communications·R GruberM Peterlik
Feb 13, 2003·Proceedings of the National Academy of Sciences of the United States of America·Dilprit BaggaSrinivasa T Reddy
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