1alpha,25-dihydroxyvitamin D(3)-induced myeloid cell differentiation is regulated by a vitamin D receptor-phosphatidylinositol 3-kinase signaling complex.
1alpha,25-dihydroxyvitamin D(3)-induced myeloid cell differentiation is regulated by a vitamin D receptor-phosphatidylinositol 3-kinase signaling complex.
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DOI：
10.1084/jem.190.11.1583
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发表时间：
1999-12-06
影响因子：
15.3
通讯作者：
Reiner, N E
中科院分区：
文献类型：
--
作者：
Hmama, Z;Nandan, D;Sly, L;Knutson, K L;Herrera-Velit, P;Reiner, N E
1α，25-二羟维生素D3（D3）促进骨髓细胞的成熟和CD 14和CD 11b的表面表达，CD 14和CD 11b是响应D3的细胞分化标志物。为了研究这些反应是如何调节的，THP-1细胞在无血清培养基中生长，并与D3孵育。这与磷脂酰肌醇3-激酶（PI 3-激酶）活性的快速和短暂增加有关。此外，D3诱导的CD 14表达可被下列物质阻断：（a）PI 3-激酶抑制剂LY 294002和渥曼青霉素;（B）PI 3-激酶p110催化亚基mRNA的反义寡核苷酸;和（c）PI 3-激酶显性失活突变体。在THP-1细胞中，LY 294002和wortmannin也可抑制D3诱导的CD 11b表达。类似地，LY 294002和渥曼青霉素抑制D3诱导的外周血单核细胞中CD 14和CD 11b的表达。与CD 14和CD 11b相反，THP-1细胞中Cdk抑制剂p21的表达不受wortmannin或LY 294002的影响。这些发现表明PI 3-激酶选择性调节D3诱导的单核细胞分化，独立于对p21的任何影响。
1α,25-dihydroxyvitamin D3 (D3) promotes the maturation of myeloid cells and surface expressions of CD14 and CD11b, markers of cell differentiation in response to D3. To examine how these responses are regulated, THP-1 cells were grown in serum-free medium and incubated with D3. This was associated with rapid and transient increases in phosphatidylinositol 3-kinase (PI 3-kinase) activity. Furthermore, induction of CD14 expression in response to D3 was abrogated by (a) the PI 3-kinase inhibitors LY294002 and wortmannin; (b) antisense oligonucleotides to mRNA for the p110 catalytic subunit of PI 3-kinase; and (c) a dominant negative mutant of PI 3-kinase. In THP-1 cells, induction of CD11b expression by D3 was also abrogated by LY294002 and wortmannin. Similarly, LY294002 and wortmannin inhibited D3-induced expression of both CD14 and CD11b in peripheral blood monocytes. In contrast to CD14 and CD11b, hormone-induced expression of the Cdk inhibitor p21 in THP-1 cells was unaffected by either wortmannin or LY294002. These findings suggest that PI 3-kinase selectively regulates D3-induced monocyte differentiation, independent of any effects on p21.