催乳素对人甲状腺细胞表面HLA-DR和CD40表达的影响

目的研究催乳素(PRL)对人甲状腺细胞表面HLA-DR和CD40表达的调节作用,以探讨PRL影响Graves'病(GD)发生、发展的可能机制.方法将传代培养的GD和对照组(取自结节性甲状腺肿和甲状腺腺瘤病变周围组织)甲状腺细胞分别经羊PRL(oPRL)、IFN-γ或IL-4以及oPRL和IFN-γ(10 U/ml)或IL-4(5 ng/ml)作用7天.利用免疫荧光染色和流式细胞仪测定其表面HLA-DR和CD40的表达.结果 oPRL(12.5-1000 ng/ml)对甲状腺细胞表面HLA-DR和CD40的表达均没有明显的直接影响.而且它对IFN-γ刺激两组甲状腺细胞及IL-4刺激GD甲状腺细胞表达HLA-DR的作用亦无明显影响.oPRL能够拮抗IFN-γ对两组甲状腺细胞表面CD40表达的刺激作用和IL-4的抑制作用.此拮抗作用与PRL的浓度有关.在200(GD:P＜0.01及P＜0.05;对照组:P＜0.05)和1000 ng/ml(P＜0.01及P＜0.05)时,它能使IFN-γ刺激的阳性细胞百分率及平均荧光强度(dMF)均显著减少.在12.5和1000 ng/ml时能使受到IL-4抑制作用的两组甲状腺细胞中CD40+细胞百分率以及在1000 ng/ml时能使GD甲状腺细胞相应的dMF明显增加(P＜0.05).对于后者,与IL-4单独作用时比,oPRL在12.5和1000 ng/ml时GD甲状腺细胞的dMF明显增加(P＜0.05).结论 PRL能够通过拮抗IFN-γ和IL-4的作用而间接影响甲状腺细胞表面CD40的表达,并且此作用与PRL的浓度有关.这可能是PRL影响GD发生、发展的一个重要机制.

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

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.