{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,7]],"date-time":"2025-11-07T18:52:04Z","timestamp":1762541524394},"reference-count":31,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[1997,6,1]],"date-time":"1997-06-01T00:00:00Z","timestamp":865123200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[1997,6,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>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\u2013induced production of IL-6\/IL-11 and studied the possible modulating effects of estrogen. rhPTH(1\u201334) and rhIL-1\u03b1 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\u2032,5\u2032-phosphorothioate (Rp-cAMPS) and H-8, inhibitors of PKA, significantly inhibited PTH-stimulated IL-6\/IL-11 production, but did not inhibit IL-1\u2013stimulated IL-6\/IL-11 production. In contrast, staurosporine and calphostin C, inhibitors of PKC, suppressed IL-1\u2013stimulated, but not PTH-stimulated, IL-6\/IL-11 production. Pretreatment of cells with 17\u03b2-estradiol (17\u03b2-E2) antagonized IL-1\u2013stimulated IL-6 production. However, PTH-stimulated IL-6 production and IL-1\u2013 and PTH-stimulated IL-11 production were not affected by 17\u03b2-E2. Similarly, 17\u03b2-E2 inhibited PMA-stimulated IL-6 production, whereas neither forskolin-stimulated IL-6\/IL-11 production nor PMA-stimulated IL-11 production was affected by 17\u03b2-E2. These results indicate that different second messengers are involved in PTH- and IL-1\u2013induced 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\u2013induced IL-6 production, which is mediated by PKC pathway, is inhibited, but PTH-induced IL-6 production and PTH\/IL-1\u2013induced IL-11 production are not inhibited by estrogen.<\/jats:p>","DOI":"10.1359\/jbmr.1997.12.6.896","type":"journal-article","created":{"date-parts":[[2006,4,26]],"date-time":"2006-04-26T22:17:42Z","timestamp":1146089862000},"page":"896-902","source":"Crossref","is-referenced-by-count":34,"title":["Involvement of Different Second Messengers in Parathyroid Hormone\u2013 and Interleukin-1\u2013Induced Interleukin-6 and Interleukin-11 Production in Human Bone Marrow Stromal Cells"],"prefix":"10.1093","volume":"12","author":[{"given":"Ghi S.","family":"Kim","sequence":"first","affiliation":[{"name":"Division of Endocrinology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chul H.","family":"Kim","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cheol S.","family":"Choi","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joong Y.","family":"Park","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ki-Up","family":"Lee","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 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