Synergistic effects of dehydroepiandrosterone and retinoic acid on granulocytic differentiation of human promyelocytic NB4 cells.
We report a novel effect of dehydroepiandrosterone (DHEA) on human granulocyte differentiation: DHEA enhances the all-trans-retinoic acid (ATRA)-induced differentiation of promyelocytic NB4 cells. DHEA (100 microM) significantly augmented the respiratory burst activity of NB4 cells treated with 1 nM ATRA, whereas DHEA alone did not induce respiratory burst activity. The protein and message expressions of p67phox, the gene for the dose-limiting component of phagocyte NADPH oxidase, were significantly enhanced by the coexistence of DHEA and ATRA. The protein expression of p47phox, another component of phagocyte NADPH oxidase, was also up-regulated by DHEA and ATRA. Moreover, the ATRA-induced increment of CCAAT/enhancer-binding protein beta (C/EBPbeta) and the reciprocal reduction in C/EBPUalpha expression were also potentiated by DHEA. In contrast, the expression of PU.1, a transcription factor reportedly involved in the basal expression of p67phox in monocytic cells, was only slightly up-regulated by DHEA and ATRA. Interestingly, DHEA sulfate (DHEAS), the sulfate ester of DHEA that exists in peripheral blood at a concentration approximately 3 orders of magnitude larger than that of DHEA, did not stimulate the ATRA-induced differentiation of NB4 cells. Thus, DHEA, but not DHEAS, plays important roles in synergy with ATRA during granulocyte differentiation of human promyelocytic NB4 cells.
Nakatsu
Masami
M
Department of Hematology, Research Institute, International Medical Center of Japan, Tokyo, Japan.
Doshi
Masaru
M
Saeki
Kumiko
K
Yuo
Akira
A
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D003687:Dehydroepiandrosterone / Q000494:pharmacology*; D004357:Drug Synergism; D006098:Granulocytes / Q000166:cytology* / Q000187:drug effects*; D006657:Histones / Q000378:metabolism; D006801:Humans; D010750:Phosphoproteins / Q000235:genetics; D014212:Tretinoin / Q000494:pharmacology*
D000276:Adjuvants, Immunologic; D000970:Antineoplastic Agents; D006657:Histones; D010750:Phosphoproteins; C079789:neutrophil cytosol factor 67K; D003687:Dehydroepiandrosterone; D014212:Tretinoin
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