Retinoic Acid Enhances the Production of IL-10 While Reducing the Synthesis of IL-12 and TNF-α from LPS-Stimulated Monocytes/Macrophages
Retinoic Acid Enhances the Production of IL-10 While Reducing the Synthesis of IL-12 and TNF-α from LPS-Stimulated Monocytes/Macrophages
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DOI：
10.1007/s10875-006-9068-5
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发表时间：
2007-01
影响因子：
9.1
通讯作者：
Xiaochuan Wang;C. Allen;M. Ballow
中科院分区：
文献类型：
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作者：
Xiaochuan Wang;C. Allen;M. Ballow
维生素A及其代谢物，例如，全反式-视黄酸（atRA）和9-顺式-视黄酸作为对体液和细胞免疫应答具有广泛免疫调节作用的化合物已经引起了相当大的关注。类维生素A对免疫系统影响的细胞和分子机制仍有待进一步明确。atRA的这些免疫调节作用可能由单核细胞和其他细胞类型产生的细胞因子介导。为了进一步了解维甲酸影响免疫应答的机制，我们检测了atRA对单核细胞产生的几种促炎和免疫调节细胞因子的影响。采用竞争性RT-PCR法检测atRA对LPS诱导的THP-1单核/巨噬细胞系和脐血单个核细胞IL-10、IL-12 p40、TNF-α、IL-18和TGF-β mRNA表达的影响。采用ELISPOT法检测IL-10和TNF-α蛋白的产生，计数产生IL-10和TNF-α的细胞数。加入atRA的细胞培养增强LPS诱导的IL-10 mRNA的表达和IL-10分泌细胞的数量从THP-1细胞和脐带血单核细胞。与此相反，atRA抑制LPS诱导的TNF-α和IL-12 p40 mRNA的表达以及TNF-α ELISPOT阳性细胞数。atRA对LPS诱导的IL-18和TGF-β mRNA表达无影响。这些结果表明，atRA可能对LPS诱导的单核细胞/巨噬细胞衍生的细胞因子具有多重作用。虽然atRA下调了促炎细胞因子，atRA可促进IL-12和TNF-α的产生，并促进IL-10的产生。atRA对这些细胞因子的影响可能在免疫和炎症反应的调节中起重要作用。
Vitamin A and its metabolites, e.g., alltrans-retinoic acid (atRA) and 9-cis-retinoic acid have attracted considerable attention as compounds that have a broad range of immune modulating effects on both humoral and cellular immune responses. The cellular and molecular mechanisms that underlie the effects of retinoids on the immune system remain to be more clearly defined. These immune modulating effects of atRA may be mediated by cytokines elaborated by monocytes and other cell types. To further understand the mechanism(s) by which retinoids affect the immune response, we examined the effects of atRA on several proinflammatory and immune modulating cytokines produced by monocytes. The effects of atRA on LPS-induced mRNA expression of IL-10, IL-12p40, TNF-α, IL-18, and TGF-β in the THP-1 monocyte/macrophage cell line and in cord blood mononuclear cells were measured by competitive RT-PCR. The ELISPOT was employed to evaluate IL-10 and TNF-α protein production enumerating the number of IL-10 and TNF-α producing cells. The addition of atRA to cell cultures potentiated the LPS-induced IL-10 mRNA expression and the number of IL-10 secreting cells from THP-1 cells and cord blood mononuclear cells. In contrast, the addition of atRA inhibited the LPS-induced TNF-α and IL-12p40 mRNA expression, and the number of ELISPOT positive cells for TNF-α. atRA did not change the LPS-induced mRNA expression of IL-18 and TGF-β. These results suggest that atRA may have multiple effects on LPS-induced monocyte/macrophage derived cytokines. While atRA downregulated the proinflammatory cytokines, e.g., IL-12 and TNF-α, the production of an immune modulating cytokine, IL-10 was enhanced by atRA. The effects of atRA on these cytokines may play an important role in the modulation of the immune and inflammatory responses.