RRC ID 61028
Author Takahashi H, Hatta Y, Iriyama N, Hasegawa Y, Uchida H, Nakagawa M, Makishima M, Takeuchi J, Takei M.
Title Induced differentiation of human myeloid leukemia cells into M2 macrophages by combined treatment with retinoic acid and 1α,25-dihydroxyvitamin D3.
Journal PLoS One
Abstract Retinoids and 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3) induce differentiation of myeloid leukemia cells into granulocyte and macrophage lineages, respectively. All-trans retinoic acid (ATRA), which is effective in the treatment of acute promyelocytic leukemia, can induce differentiation of other types of myeloid leukemia cells, and combined treatment with retinoid and 1,25(OH)2D3 effectively enhances the differentiation of leukemia cells into macrophage-like cells. Recent work has classified macrophages into M1 and M2 types. In this study, we investigated the effect of combined treatment with retinoid and 1,25(OH)2D3 on differentiation of myeloid leukemia THP-1 and HL60 cells. 9-cis Retinoic acid (9cRA) plus 1,25(OH)2D3 inhibited proliferation of THP-1 and HL60 cells and increased myeloid differentiation markers including nitroblue tetrazolium reducing activity and expression of CD14 and CD11b. ATRA and the synthetic retinoic acid receptor agonist Am80 exhibited similar effects in combination with 1,25(OH)2D3 but less effectively than 9cRA, while the retinoid X receptor agonist HX630 was not effective. 9cRA plus 1,25(OH)2D3 effectively increased expression of M2 macrophage marker genes, such as CD163, ARG1 and IL10, increased surface CD163 expression, and induced interleukin-10 secretion in myeloid leukemia cells, while 9cRA alone had weaker effects on these phenotypes and 1,25(OH)2D3 was not effective. Taken together, our results demonstrate selective induction of M2 macrophage markers in human myeloid leukemia cells by combined treatment with 9cRA and 1,25(OH)2D3.
Volume 9(11)
Pages e113722
Published 2014
DOI 10.1371/journal.pone.0113722
PII PONE-D-14-37744
PMID 25409436
PMC PMC4237509
MeSH Antigens, CD / genetics Antigens, CD / metabolism Antigens, Differentiation, Myelomonocytic / genetics Antigens, Differentiation, Myelomonocytic / metabolism Antineoplastic Agents / toxicity* Arginase / genetics Arginase / metabolism CD11b Antigen / genetics CD11b Antigen / metabolism Cell Differentiation / drug effects* Cell Proliferation / drug effects Gene Expression Regulation, Neoplastic HL-60 Cells Humans Interleukin-10 / genetics Interleukin-10 / metabolism Leukemia, Promyelocytic, Acute / metabolism Leukemia, Promyelocytic, Acute / pathology Lipopolysaccharide Receptors / genetics Lipopolysaccharide Receptors / metabolism Macrophages / cytology Macrophages / drug effects Macrophages / metabolism Receptors, Cell Surface / genetics Receptors, Cell Surface / metabolism Tretinoin / toxicity* Vitamin D / analogs & derivatives* Vitamin D / toxicity
Human and Animal Cells THP-1(RCB1189)