1,25-Dihydroxyvitamin D3 suppresses the expression of the VCAM-1 receptor, VLA-4 in human leukemic HL-60 cells.
Very late antigen-4 (VLA-4) is the complex with alpha4 and beta1 integrins, which is the receptors to fibronectin and VCAM-1. We evaluate the effect of 1,25(OH)2D3 on the expression of VLA-4 in human leukemic HL-60, U937 cells and human melanoma A375 cells. Flow cytometric analysis demonstrate that the expression of alpha4 integrin is negatively regulated in the cell lines we studied. The expression of beta1 integrin is also decreased in HL-60 and U937 cells. The mRNA expression of alpha4 integrin is significantly decreased by the treatment with 1,25(OH)2D3, whereas 1,25(OH)2D3 does not alter the expression of beta1 mRNA. The adhesion assay demonstrate that the number of adherent cells treated with 1, 25(OH)2D3 is significantly lower than that untreated on VCAM-1-coated wells. Because VCAM-1 is highly expressed in the endothelial cells, it is possible that 1,25(OH)2D3 prevents the attachment of the cells from the endothelial cells in vivo.
Department of Geriatrics, Endocrinology, and Metabolism, Shinshu University School of Medicine, Matsumoto, Japan.
A
A
Kaneko
S
S
Suzuki
M
M
Hara
J
J
Mori
M
M
Kumagai
H
H
Yajima
K
K
Yamashita
T
T
Kakizawa
M
M
Yamazaki
T
T
Takeda
T
T
Miyamoto
K
K
Ichikawa
K
K
Hashizume
D015703:Antigens, CD / Q000096:biosynthesis / Q000235:genetics; D002117:Calcitriol / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D018922:HL-60 Cells; D006801:Humans; D039441:Integrin alpha4; D039041:Integrin alpha4beta1; D019012:Integrin beta1 / Q000096:biosynthesis / Q000235:genetics; D016023:Integrins / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics; D015473:Leukemia, Promyelocytic, Acute / Q000378:metabolism*; D008024:Ligands; D012333:RNA, Messenger / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D016201:Receptors, Lymphocyte Homing / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics; D016029:Receptors, Very Late Antigen / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D020298:U937 Cells; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism* / Q000502:physiology
D015703:Antigens, CD; D039041:Integrin alpha4beta1; D019012:Integrin beta1; D016023:Integrins; D008024:Ligands; D012333:RNA, Messenger; D016201:Receptors, Lymphocyte Homing; D016029:Receptors, Very Late Antigen; D019010:Vascular Cell Adhesion Molecule-1; D039441:Integrin alpha4; D002117:Calcitriol