GLUCOCORTICOIDS INHIBIT ACTIVATION-DEPENDENT EXPRESSION OF COSTIMULATORY MOLECULE B7-1 IN HUMAN MONOCYTES

Background Glucocorticoids act as immunosuppressive drugs mainly via t heir effects on antigen-presenting cells. They are known to influence production of cytokines as well as expression of cell surface molecule s. B7 molecules belong to the most important costimulatory signals for T-cell activation during transplant rejection. They are expressed on antigen-presenting cells and up-regulated during the immune response. We studied the influence of glucocorticoids on the regulation of these accessory signals. Methods. Human monocytes were purified from periph eral blood of healthy volunteers by centrifugal counterflow elutriatio n. Activation-dependent transcription and expression of B7-1 (CD80) an d B7-2 (CD86) were detected by reverse transcription-polymerase chain reaction and flow cytometry in the absence or presence of glucocortico ids. Results. The expression pattern of B7-1 and B7-2 on monocytes dep ends on the type of stimulation. Activation by interferon-gamma induce s both B7-1 and B7-2, whereas cAMP exclusively up-regulates B7-2, Gluc ocorticoids selectively inhibit the expression of B7-1 while leaving B 7-2 unaffected. The effect occurs at concentrations that are reached d uring therapeutical application of the substances in humans. It is med iated via the cytoplasmic glucocorticoid receptor, as it can be abroga ted by the glucocorticoid receptor antagonist RU38486. Inhibition of B 7-1 occurs at the transcriptional level. Up-regulation of the molecule can similarly be inhibited by hydrocortisone, prednisolone, and dexam ethasone at equipotent doses. Conclusions. Inhibition of the up-regula tion of B7-1 by glucocorticoids is a previously unknown mechanism of a ction of these substances and may relevantly contribute to their effec ts as immunosuppressive drugs.