Effects of prolactin on HLA-DR and CD40 expressions by human thyrocytes

Abstract

Objective: To study the effects of prolactin (PRL) on HLA-DR and CD40 expressions by human thyrocytes, and to investigate the possible mechanisms for PRL to affect the development of Graves' disease (GD).

Methods: Thyrocytes in secondary culture, which were from GD thyroid glands and the tissues adjacent to the lesions of multinodular goiter and adenoma (control group), were treated respectively with ovine PRL (oPRL), interferon-gamma (IFN-gamma), interlukin-4 (IL-4) and oPRL plus IFN-gamma (10 U/ml) or IL-4 (5 ng/ml) for 7 days. HLA-DR and CD40 expressions on the thyrocytes were determined by immunofluorescent staining and flow cytometry.

Results: oPRL (12.5 ng/ml-1000 ng/ml) had no significant direct effect on HLA-DR or CD40 expression. It did not significantly affect the stimulation of HLA-DR expressions on the two groups of thyrocyte treated with IFN-gamma or on GD thyrocytes treated with IL-4. oPRL could antagonize the stimulation of CD40 expressions by IFN-gamma and the inhibition by IL-4 on both groups of thyrocytes. The antagonizing effects were related to the concentrations of PRL. IFN-gamma-stimulated percentages of CD40+ thyrocytes and delta mean fluorescence intensity (dMF) in both thyrocyte sources were significantly reduced in the presence of 200 ng/ml oPRL (both GD and

Control: P < 0.01 and P < 0.05, respectively;

Control: P < 0.05) and 1000 ng/ml oPRL (GD: P < 0.01;

Control: P < 0.05). oPRL caused significant increasing in IL-4-inhibited percentages of CD40+ cells from the two groups of thyrocytes at 12.5 ng/ml and 1000 ng/ml and dMF from GD thyrocytes at 1000 ng/ml (P < 0.05).

Conclusions: PRL can exert indirect effects on CD40 expressions on thyrocytes by antagonizing the modulatory actions of IFN-gamma and IL-4 with dose-related effects. This may be one important mechanism for PRL to affect the development of GD.