Synergism of glucocorticoids with granulocyte macrophage colony stimulating factor (GM-CSF) but not interferon gamma (IFN-gamma) or interleukin-4 (IL-4) on induction of HLA class II expression on human monocytes.
Peripheral blood monocytes from up to 13 normal donors were stimulated with the cytokines interferon gamma (IFN-gamma), interleukin 4 (IL-4) and granulocyte macrophage-colony stimulating factor (GM-CSF) in the presence or absence of dexamethasone (Dex), and the effects on HLA class II (HLA-DR, DP and DQ) expression studied. Dex markedly augmented HLA-DR, DP and DQ levels induced by GM-CSF, in all samples tested. Particularly striking were the effects on HLA-DQ expression, since stimulation with a combination of Dex and GM-CSF induced markedly higher levels of HLA-DQ antigen than stimulation with IFN-gamma. Northern blot analysis of samples treated for 40 hours with Dex and GM-CSF indicated that levels of DR alpha, DP alpha and DQ alpha mRNA were also increased. In contrast, despite variation between individual donors, in general Dex weakly inhibited both constitutive and IFN-gamma- or IL-4-induced HLA-DR expression. Variability in the responsiveness of monocytes purified from individual donors to each cytokine was also observed. GM-CSF was less potent than IFN-gamma and IL-4, enhancing HLA class II expression in only seven of 13 donors tested, whereas in the presence of Dex all donors responded to GM-CSF. The differential effects of glucocorticoids in vitro suggest that these cytokines induce HLA class II expression by different mechanisms.
Sadeghi
R
R
Charing Cross Sunley Research Centre, Hammersmith, London.
Hawrylowicz
C M
CM
Chernajovsky
Y
Y
Feldmann
M
M
D001483:Base Sequence; D016207:Cytokines / Q000502:physiology*; D003907:Dexamethasone / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000502:physiology; D006681:HLA-D Antigens / Q000235:genetics*; D006682:HLA-DP Antigens / Q000235:genetics; D006683:HLA-DQ Antigens / Q000235:genetics; D006684:HLA-DR Antigens / Q000235:genetics; D006801:Humans; D007371:Interferon-gamma / Q000502:physiology; D015847:Interleukin-4 / Q000502:physiology; D008969:Molecular Sequence Data; D009000:Monocytes / Q000276:immunology*; D012333:RNA, Messenger / Q000378:metabolism
D016207:Cytokines; D006681:HLA-D Antigens; D006682:HLA-DP Antigens; D006683:HLA-DQ Antigens; D006684:HLA-DR Antigens; D012333:RNA, Messenger; D015847:Interleukin-4; D003907:Dexamethasone; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor