Synergistic Effect of 1,25-Dihydroxyvitamin D3 and Retinoic Acid in Inducing U937 Cell Differentiation.
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概要
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We examined the effects of retinoic acid (RA), 1, 25-dihydroxyvitamin D3 (1, 25-(OH)2D3), and its synthetic analogue, 22-oxa-1, 25-(OH)2D3, on differentiation of U937 cells by studying the cellular growth, surface marker expression and cytosolic free Ca2+ concentration ([Ca2+]i). RA inhibited cellular growth but did not induce expression of Mo2 (CD14), a monocyte/macrophage specific surface marker. To the contrary, 1, 25-(OH)2D3 did not inhibit cellular growth, but increased CD14-positive cells. Simultaneous addition of 1, 25-(OH)2D3 and RA had no additive effect on cellular growth inhibition or CD14 expression. With regard to [Ca2+]i, however, 5 days' incubation with either of them increased the basal [Ca2+]i level and induced U937 cells to respond to formyl-methionyl-leucyl-phenylalanine (FMLP). When the cells were incubated with both 10-6M RA and 10-8M 1, 25-(OH)2D3, basal [Ca2+]i was higher and FMLP caused a greater increase in [Ca2+]i than when only RA or 1, 25-(OH)2D3 was added. These data suggest that RA and 1, 25-(OH)2D3 induce monocytoid differentiation in U937 cells through different pathways and act synergistically in the differentiation process. The 22-oxa-1, 25-(OH)2D3 induced CD14 expression, basal [Ca2+]i increase and [Ca2+]i response to FMLP, but did not cause cellular growth inhibition in U937 cells, and in these points, 22-oxa-1, 25-(OH)2D3 exhibited no significantly different effects from 1, 25-(OH)2D3. Thus, 22-oxa-1, 25-(OH)2D3 has the same potent activity as 1, 25-(OH)2D3 in inducing differentiation of U937 cells.
- 財団法人 学会誌刊行センターの論文
著者
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Seino Yoshiki
Department Of Pediatrics
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Yamaoka Kanji
Department Of Pediatrics Osaka Prefectural General Hospital
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Okada Shintaro
Department Of Developmental Medicine (pediatrics) D-5 Osaka University Graduate School Of Medicine.
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Tanaka Yoshihisa
Department Of Electronics Faculty Of Industrial Arts Kyoto Technical University
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Shima Masaaki
Department Of Developmental Medicine (pediatrics) D-5 Osaka University Graduate School Of Medicine
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OKADA Shintaro
Department of Pediatrics, Osaka University School of Medicine
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YAMAOKA Kanji
Department of Pediatrics, Osaka University School of Medicine
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SHIMA Masaaki
Department of Pediatrics, Osaka University School of Medicine
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SEINO Yoshiki
Department of Pediatrics, University of Okayama School of Medicine
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