Dabelic Sanja, Supraha Sandra, Dumic Jerka
Department of Biochemistry and Molecular Biology, Faculty of Pharmacy and Biochemistry, University of Zagreb, Croatia.
Biochim Biophys Acta. 2006 Apr;1760(4):701-9. doi: 10.1016/j.bbagen.2005.11.020. Epub 2005 Dec 20.
During the last few decades, the effects of immunomodulatory drugs on numerous molecules and biological processes have been widely studied. Nevertheless, the relationship between immunomodulatory drugs and lectin expression/function is still to be elucidated. In this study, we used THP-1-derived macrophages to investigate the effects of non-steroidal anti-inflammatory drugs (aspirin and indomethacin) and glucocorticoids (hydrocortisone and dexamethasone) on galectin-3, a multifunctional beta-galactoside binding lectin, which in general acts as a strong pro-inflammatory signal. The results showed that all immunomodulatory drugs applied in clinically relevant doses affect both the gene (LGALS3) and protein expression level of galectin-3. The provoked changes on protein level are qualitatively and quantitatively different comparing to the effects on galectin-3 mRNA level, and depend on the differentiation state of the cell, drug type and applied concentration as well as on time of the exposure. Our data revealed galectin-3 as a new target molecule of immunomodulatory drugs, thus suggesting an additional pathway of their action on immune response.
在过去几十年里,免疫调节药物对众多分子和生物学过程的影响已得到广泛研究。然而,免疫调节药物与凝集素表达/功能之间的关系仍有待阐明。在本研究中,我们使用THP-1来源的巨噬细胞来研究非甾体抗炎药(阿司匹林和吲哚美辛)和糖皮质激素(氢化可的松和地塞米松)对半乳糖凝集素-3的影响,半乳糖凝集素-3是一种多功能的β-半乳糖苷结合凝集素,通常作为一种强烈的促炎信号。结果表明,所有以临床相关剂量应用的免疫调节药物都会影响半乳糖凝集素-3的基因(LGALS3)和蛋白质表达水平。与对半乳糖凝集素-3 mRNA水平的影响相比,蛋白质水平上引发的变化在质量和数量上都有所不同,并且取决于细胞的分化状态、药物类型、应用浓度以及暴露时间。我们的数据揭示了半乳糖凝集素-3是免疫调节药物的一个新的靶分子,从而提示了它们作用于免疫反应的一条额外途径。