Interaction between galectin-3 and FcγRII induces down-regulation of IL-5 gene:: implication of the promoter sequence IL-5REIII

Interaction between galectin-3 and FcγRII induces down-regulation of IL-5 gene:: implication of the promoter sequence IL-5REIII
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DOI:
10.1093/glycob/10.3.237
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发表时间:
2000-03-01
期刊:
影响因子:
4.3
通讯作者:
Lahoz, C
Lahoz, C
中科院分区:
生物学3区
文献类型:
--
作者:
Cortegano, I;del Pozo, V;Lahoz, C

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我们之前的工作证明了半乳凝素-3(一种β-半乳糖苷结合动物凝集素)能够抑制不同细胞类型中IL-5基因的表达,但凝集素与细胞的相互作用以及抑制过程的途径尚不清楚。这项工作的目的之一是研究半乳糖凝集素-3的细胞配体。我们已经证明,半乳糖凝集素-3可以结合低亲和力IgG受体(Fc γ RII或CD 32),通过使用不同的实验方法,如流式细胞术,融合蛋白GST技术,并与Fc γ RII缺陷小鼠模型。为了进一步分析Fc γ RII和半乳糖凝集素3之间的相互作用及其在IL-5基因下调中的意义,我们使用Fc γ RII缺陷小鼠。当来自这些小鼠的PBMC与半乳糖凝集素-3孵育时,IL-5基因的表达没有变化。然而,当来自野生型小鼠和Fc γ RIII缺陷小鼠的PBMC与半乳糖凝集素3孵育时,IL-5基因表达下调。最后,我们研究了IL-5基因启动子中负调控序列的含义。在半乳糖凝集素3的存在下,与IL-5 REIII区域形成DNA-蛋白质复合物。当使用不相关的寡核苷酸时未观察到这种复合物,因此,半乳糖凝集素3诱导激活与IL-5 REIII结合的转录因子的途径,这种相互作用能够抑制IL-5基因转录。
Our previous work demonstrated the capacity of galectin-3 (a P-galactoside binding animal lectin) to inhibit IL-5 gene expression in different cell types, but the interaction of lectin with the cells and the pathways for tbe inhibition process are unknown. One of the purposes of this work was to study the cellular ligand for galectin-3. We have demonstrated that galectin-3 can bind to the low affinity IgG receptor (Fc gamma RII or CD32) by using different experimental approaches, such as flow cytometry, fusion protein GST technology, and with a model of Fc gamma RII-deficient mice. To further analyze the interaction between Fc gamma RII and galectin3, and its implication in IL-5 gene down-regulation we used Fc gamma RII-deficient mice. When PBMC from these mice were incubated with galectin-3, the expression of the IL-5 gene was unchanged. However, when PBMC from wild type mice and Fc gamma RIII-deficient mice were incubated with galectin3, IL-5 gene expression was down-regulated, Finally, we studied the implication of the negative regulatory sequence in the IL-5 gene promoter. In the presence of galectin3, a DNA-protein complex was formed with the IL-5REIII region. This complex was not observed when unrelated oligonucleotide was used, So, galectin3 induces a pathway, which activates a transcription factor that binds to IL-5REIII, This interaction is capable of inhibiting IL-5 gene transcription.