1α,25-Dihydroxyvitamin D3–Induced Myeloid Cell Differentiation Is Regulated by a Vitamin D Receptor–Phosphatidylinositol 3-Kinase Signaling Complex
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 w...
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| Format: | Online |
| Language: | English |
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The Rockefeller University Press
1999
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| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2195730/ |
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pubmed-21957302008-04-16 1α,25-Dihydroxyvitamin D3–Induced Myeloid Cell Differentiation Is Regulated by a Vitamin D Receptor–Phosphatidylinositol 3-Kinase Signaling Complex Hmama, Zakaria Nandan, Devki Sly, Laura Knutson, Keith L. Herrera-Velit, Patricia Reiner, Neil E. Original Article 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. The Rockefeller University Press 1999-12-06 /pmc/articles/PMC2195730/ /pubmed/10587349 Text en © 1999 The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/). |
| repository_type |
Open Access Journal |
| institution_category |
Foreign Institution |
| institution |
US National Center for Biotechnology Information |
| building |
NCBI PubMed |
| collection |
Online Access |
| language |
English |
| format |
Online |
| author |
Hmama, Zakaria Nandan, Devki Sly, Laura Knutson, Keith L. Herrera-Velit, Patricia Reiner, Neil E. |
| spellingShingle |
Hmama, Zakaria Nandan, Devki Sly, Laura Knutson, Keith L. Herrera-Velit, Patricia Reiner, Neil E. 1α,25-Dihydroxyvitamin D3–Induced Myeloid Cell Differentiation Is Regulated by a Vitamin D Receptor–Phosphatidylinositol 3-Kinase Signaling Complex |
| author_facet |
Hmama, Zakaria Nandan, Devki Sly, Laura Knutson, Keith L. Herrera-Velit, Patricia Reiner, Neil E. |
| author_sort |
Hmama, Zakaria |
| title |
1α,25-Dihydroxyvitamin D3–Induced Myeloid Cell Differentiation Is Regulated by a Vitamin D Receptor–Phosphatidylinositol 3-Kinase Signaling Complex |
| title_short |
1α,25-Dihydroxyvitamin D3–Induced Myeloid Cell Differentiation Is Regulated by a Vitamin D Receptor–Phosphatidylinositol 3-Kinase Signaling Complex |
| title_full |
1α,25-Dihydroxyvitamin D3–Induced Myeloid Cell Differentiation Is Regulated by a Vitamin D Receptor–Phosphatidylinositol 3-Kinase Signaling Complex |
| title_fullStr |
1α,25-Dihydroxyvitamin D3–Induced Myeloid Cell Differentiation Is Regulated by a Vitamin D Receptor–Phosphatidylinositol 3-Kinase Signaling Complex |
| title_full_unstemmed |
1α,25-Dihydroxyvitamin D3–Induced Myeloid Cell Differentiation Is Regulated by a Vitamin D Receptor–Phosphatidylinositol 3-Kinase Signaling Complex |
| title_sort |
1α,25-dihydroxyvitamin d3–induced myeloid cell differentiation is regulated by a vitamin d receptor–phosphatidylinositol 3-kinase signaling complex |
| description |
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. |
| publisher |
The Rockefeller University Press |
| publishDate |
1999 |
| url |
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2195730/ |
| _version_ |
1611432222783438848 |