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• W2040905054 startingPage "896" @default.
• W2040905054 abstract "Abstract Previous studies have suggested that increased secretion of bone active cytokines, such as interleukin‐6 (IL‐6) and interleukin‐11 (IL‐11), from osteoblasts and stromal cells play a pivotal role in the activation of osteoclasts and the genesis of osteoporosis. Various systemic and local factors can stimulate IL‐6/IL‐11 production, but the intracellular mechanism for such stimulation is largely unknown. In this study, we characterized the second messenger signaling in parathyroid hormone (PTH)‐ and IL‐1–induced production of IL‐6/IL‐11 and studied the possible modulating effects of estrogen. rhPTH(1–34) and rhIL‐1α dose‐dependently stimulated IL‐6 and IL‐11 production from human bone marrow stromal cells (hBMSCs). Agonists for protein kinase A (PKA) (forskolin), and protein kinase C (PKC) (phorbol 12‐myristate 13‐acetate; PMA) also stimulated IL‐6/IL‐11 production. Rp‐diastereoisomer of adenosine cyclic 3′,5′‐phosphorothioate (Rp‐cAMPS) and H‐8, inhibitors of PKA, significantly inhibited PTH‐stimulated IL‐6/IL‐11 production, but did not inhibit IL‐1–stimulated IL‐6/IL‐11 production. In contrast, staurosporine and calphostin C, inhibitors of PKC, suppressed IL‐1–stimulated, but not PTH‐stimulated, IL‐6/IL‐11 production. Pretreatment of cells with 17β‐estradiol (17β‐E 2 ) antagonized IL‐1–stimulated IL‐6 production. However, PTH‐stimulated IL‐6 production and IL‐1– and PTH‐stimulated IL‐11 production were not affected by 17β‐E 2 . Similarly, 17β‐E 2 inhibited PMA‐stimulated IL‐6 production, whereas neither forskolin‐stimulated IL‐6/IL‐11 production nor PMA‐stimulated IL‐11 production was affected by 17β‐E 2 . These results indicate that different second messengers are involved in PTH‐ and IL‐1–induced IL‐6 and IL‐11 production by hBMSCs: PTH and IL‐1 stimulate IL‐6/IL‐11 production via a PKA‐dependent and PKC‐dependent pathway, respectively. Furthermore, our results suggest that regulation of cytokine production by estrogen in hBMSCs is selective; only the IL‐1–induced IL‐6 production, which is mediated by PKC pathway, is inhibited, but PTH‐induced IL‐6 production and PTH/IL‐1–induced IL‐11 production are not inhibited by estrogen." @default.
• W2040905054 created "2016-06-24" @default.
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• W2040905054 date "1997-06-01" @default.
• W2040905054 modified "2023-10-10" @default.
• W2040905054 title "Involvement of Different Second Messengers in Parathyroid Hormone- and Interleukin-1-Induced Interleukin-6 and Interleukin-11 Production in Human Bone Marrow Stromal Cells" @default.
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• W2040905054 doi "https://doi.org/10.1359/jbmr.1997.12.6.896" @default.
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