1,25(OH)2D3 regulates c-myc mRNA levels in tonsillar T lymphocytes.
The effects of 1,25(OH)2D3 on proliferation, c-myc mRNA levels and 1,25(OH)2D3 receptor expression in activated tonsillar T lymphocytes were studied. Activation of resting T cells with phytohaemagglutinin (PHA) for 72 hr led to an increase in proliferation, c-myc mRNA levels and to induction of 1,25(OH)2D3 receptor expression. However, when activation was carried out in the presence of 1,25(OH)2D3, there was inhibition of PHA-stimulated proliferation and c-myc mRNA levels. Increased cell proliferation, c-myc mRNA expression and 1,25(OH)2D3 receptor number were also observed, albeit to a lesser extent, when T cells were stimulated by phorbol myristate acetate (PMA), anti-CD3 antibody or A23187. However, in these cases 1,25(OH)2D3 was unable to prevent increased proliferation or c-myc mRNA expression. PMA and anti-CD3 used in combination produced similar or greater changes in proliferation, c-myc mRNA levels, 1,25(OH)2D3 receptor expression and responsiveness to the hormone when compared to PHA alone. Thus the inhibition of c-myc expression in activated T lymphocytes by 1,25(OH)2D3 can be related to its anti-proliferative effects. Moreover this inhibition seems to be dependent on the level of 1,25(OH)2D3 receptor expression, which in turn appears to be related to the degree of cell activation.
Karmali
R
R
Department of Medicine, Middlesex Hospital, London, U.K.
Hewison
M
M
Rayment
N
N
Farrow
S M
SM
Brennan
A
A
Katz
D R
DR
O'Riordan
J L
JL
D002117:Calcitriol / Q000502:physiology*; D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000276:immunology*; D016259:Genes, myc / Q000276:immunology*; D006801:Humans; D008213:Lymphocyte Activation / Q000235:genetics; D014066:Palatine Tonsil / Q000276:immunology*; D012333:RNA, Messenger / Q000032:analysis; D013601:T-Lymphocytes / Q000276:immunology*
D012333:RNA, Messenger; D002117:Calcitriol