BIOCHEMICAL-CHARACTERIZATION OF A GLUCOCORTICOID-INDUCED MEMBRANE-PROTEIN (RM3 1) IN HUMAN MONOCYTES AND ITS APPLICATION AS MODEL SYSTEM FOR RANKING GLUCOCORTICOID POTENCY/
P. Hogger et al., BIOCHEMICAL-CHARACTERIZATION OF A GLUCOCORTICOID-INDUCED MEMBRANE-PROTEIN (RM3 1) IN HUMAN MONOCYTES AND ITS APPLICATION AS MODEL SYSTEM FOR RANKING GLUCOCORTICOID POTENCY/, Pharmaceutical research, 15(2), 1998, pp. 296-302
Purpose. Upon glucocorticoid stimulation, human mononuclear leucocytes
express an antigen, RM3/1, which characterizes a subpopulation of hum
an monocytes and macrophages evolving in late phase of inflammation. W
e investigated biochemical properties of the RM3/1 antigen and correla
tions between antigen expression and glucocorticoid potency. Methods.
Biochemical properties were analyzed after solubilization by immunoaff
inity methods and SDS-PAGE. Results. Induction of the RM3/1 antigen is
a glucocorticoid receptor mediated process, in contrast, inflammatory
mediators such as LPS or TPA were not able to upregulate RM3/1 expres
sion. After SDS-PAGE, the antigen appeared as a 130 kDa (nonreduced)/1
50 kDa (reduced) glycoprotein with a 25 kDa N-linked glycoportion. The
interdependence between antigen density and glucocorticoid efficacy w
as assessed by calculation of relative antigen expression induced by d
examethasone, fluticasone propionate, budesonide, triamcinolone aceton
ide, flunisolide, beclomethasone, prednisolone and triamcinolone. Rela
tive antigen expression was significantly correlated with the relative
receptor affinity of the glucocorticoid. Conclusions. We described bi
ochemical properties of the glucocorticoid-induced protein RM3/1. Thou
gh the precise role of the RM3/1 antigen in the antiinflammatory proce
ss is not fully understood yet, an useful application of the induced e
xpression could already be demonstrated for pre-clinical screening of
glucocorticoid potency.