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Regulation of Interleukin‐6 Production by Prostaglandin E 2 in Fetal Rat Osteoblasts: Role of Protein Kinase A Signaling Pathway
Author(s) -
Millet Isabelle,
Mccarthy Thomas L.,
Vignery AgnÈS
Publication year - 1998
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1359/jbmr.1998.13.7.1092
Subject(s) - prostaglandin e2 , osteoblast , signal transduction , endocrinology , prostaglandin e2 receptor , medicine , microbiology and biotechnology , cytokine , protein kinase a , eicosanoid , prostaglandin e , kinase , chemistry , biology , receptor , biochemistry , enzyme , arachidonic acid , in vitro , agonist
Prostaglandin E 2 (PGE 2 ) 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 PGE 2 induces IL‐6 in the bone environment, this study was designed to investigate whether PGE 2 regulated IL‐6 expression by osteoblasts. Here we demonstrate that PGE 2 is a potent inducer of IL‐6 production by fetal rat osteoblasts and synergizes with lipopolysaccharide to enhance IL‐6. We show that PGE 2 stimulates the activity of the IL‐6 promoter in osteoblasts, suggesting that PGE 2 controls IL‐6 gene expression at least at the transcriptional level. Moreover, we show that PGE 2 ‐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 PGE 2 involves the cAMP–PKA signaling pathway to regulate IL‐6 gene expression in osteoblasts.