Effect of TGF-beta on interferon-gamma-induced HLA-DR expression in human retinal pigment epithelial cells.
Effect of TGF-beta on interferon-gamma-induced HLA-DR expression in human retinal pigment epithelial cells.
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发表时间：
1994-12
影响因子：
4.4
通讯作者：
K. Gabrielian;R. Osuský;B. D. Sippy;S. Ryan;D. Hinton
中科院分区：
文献类型：
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作者：
K. Gabrielian;R. Osuský;B. D. Sippy;S. Ryan;D. Hinton
视网膜色素上皮（RPE）细胞在干扰素γ（IFN-γ）刺激下表达人类白细胞抗原（HLA）-DR（II类）抗原，并可能具有局部抗原呈递的能力。作者研究了转化生长因子-β（TGF-β）（一种通常在眼睛中发现的细胞因子）对体外这些免疫调节分子表达的影响，并试图确定这种细胞因子的作用机制。方法人RPE细胞在IFN-γ存在下培养，然后进行HLA-DR抗原的免疫组化染色。TGF-β 1或TGF-β 2与IFN-γ同时或在IFN-γ处理3天后加入。在平行实验中，在用IFN-γ或TGF-β刺激之前，用4-佛波醇-12肉豆蔻酸酯-13乙酸酯（PMA）、星形孢菌素或钙磷蛋白C预处理RPE细胞。通过荧光激活细胞分选进行定量分析。结果IFN-γ诱导RPE细胞HLA-DR表达。TGF-β 1和TGF-β 2都能够抑制这种作用。这些TGF-β的抑制作用通过PMA或calphostin C预处理而增强。在用IFN-γ刺激之前用PMA预处理细胞下调HLA-DR表达。星形孢菌素预处理抑制IFN-γ刺激的RPE细胞的HLA-DR表达，但这与TGF-β无关。结论：作者得出结论，TGF-β 1和TGF-β 2强烈抑制IFN-γ诱导的人RPE细胞II类抗原上调。钙磷蛋白C、星形孢菌素和PMA处理对这些IFN-γ和TGF-β作用的调节表明蛋白激酶C途径的参与。
PURPOSE Retinal pigment epithelial (RPE) cells express human leukocyte antigen (HLA)-DR (class II) antigens when stimulated with interferon gamma (IFN-gamma) and may be capable of local antigen presentation. The authors examined the effect of transforming growth factor-beta (TGF-beta), a cytokine normally found in the eye, on the expression of these immunoregulatory molecules in vitro and attempted to determine the mechanism by which this cytokine acts. METHODS Human RPE cells were cultured in the presence of IFN-gamma and then stained immunohistochemically for HLA-DR antigens. TGF-beta 1 or TGF-beta 2 was added simultaneously with IFN-gamma or after 3 days of IFN-gamma treatment. In parallel experiments, RPE cells were pretreated with 4-phorbol-12 myristate-13 acetate (PMA), staurosporine, or calphostin C before stimulation with IFN-gamma or TGF-beta. Quantitative analysis was performed by fluorescence-activated cell sorting. RESULTS IFN-gamma induced HLA-DR expression on RPE cells. Both TGF-beta 1 and TGF-beta 2 were able to inhibit this effect. These inhibitory effects of TGF-beta were augmented by pretreatment with either PMA or calphostin C. Pretreatment of the cells with PMA before stimulation with IFN-gamma downregulated HLA-DR expression. Staurosporine pretreatment suppressed HLA-DR expression by IFN-gamma-stimulated RPE cells, but this was not additive with TGF-beta. CONCLUSIONS The authors conclude that TGF-beta 1 and TGF-beta 2 strongly inhibit the IFN-gamma-induced upregulation of class II antigens on human RPE cells. The modulation of these IFN-gamma and TGF-beta effects by calphostin C, staurosporine, and PMA treatment suggests involvement of the protein kinase C pathway.