1,25-Dihydroxyvitamin D3 decreases expression of HLA class II molecules in a melanoma cell line.
An HLA class II-positive melanoma cell line, DU-Mel 17, was treated with three compounds known to induce differentiation in various cell lines. Neither retinoic acid nor dibutyryl cAMP altered levels of DR alpha mRNA, but 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) significantly decreased the level of DR alpha mRNA 48 h after treatment. Optimal effect of the hormone on DR alpha mRNA was reached by 72 h. DU-Mel 17 cells were responsive to 1,25(OH)2D3 in a dose-dependent manner, and a reduction in DR alpha mRNA was seen at concentrations as low as 5 x 10(-13) M. The action of 1,25(OH)2D3 on DR alpha mRNA levels was dependent on protein synthesis as evidenced by inhibition of its effect upon addition of cycloheximide. Both DR and DQ protein levels on the surface of DU-Mel 17 were beginning to decline by 72 h after 1,25(OH)2D3 treatment, and by 96 h these proteins were decreased by 65%. 1,25(OH)2D3 was not capable of altering expression of class II molecules on three different class II-positive B lymphoblastoid cell lines, although one of these lines was shown to express the receptor for 1,25(OH)2D3. These findings are important because 1) there is no known physiologic regulator that actively down-regulates class II molecules that are present in and/or on cells, 2) levels of mRNA derived from a very limited number of genes are known to be altered by 1,25(OH)2D3, and 3) they support the contention that 1,25(OH)2D3 may alter the differentiation state of these cells and the activity of the normal counterpart of these cells in an immune response.
Carrington
M N
MN
Department of Microbiology and Immunology, Duke University Medical Center, Durham, NC 27710.
Tharp-Hiltbold
B
B
Knoth
J
J
Ward
F E
FE
D002117:Calcitriol / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D004306:Dose-Response Relationship, Immunologic; D006681:HLA-D Antigens / Q000378:metabolism*; D006684:HLA-DR Antigens / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008546:Melanoma, Experimental / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000096:biosynthesis; D014158:Transcription, Genetic / Q000187:drug effects
D006681:HLA-D Antigens; D006684:HLA-DR Antigens; D012333:RNA, Messenger; D002117:Calcitriol