Ziram, a zinc dithiocarbamate is widely used worldwide as a fungicide in agriculture. In order to investigate ziram-induced changes in macrophage functions and polarization, human monocytes-derived macrophages in culture were treated with ziram at 0.01–10 μmol.L⁻¹ for 4–24 h. To characterize zinc involvement in these changes, we also determined the effects of disulfiram alone (dithiocarbamate without zinc) or in co-incubation with ZnSO₄. We have shown that ziram and disulfiram at 0.01 μmol.L⁻¹ increased zymosan phagocytosis. In contrast, ziram at 10 μmol.L⁻¹ completely inhibited this phagocytic process, the oxidative burst triggered by zymosan and the production of TNF-α, IL-1β, IL-6, and CCL2 triggered by LPS. Disulfiram had the same effects on these macrophages functions only when combined with zinc (10 μmol.L⁻¹). In contrast, at 10 μmol.L⁻¹ ziram and zinc associated-disulfiram induced expression of several antioxidants genes HMOX1, SOD2, and catalase, which could suggest the induction of oxidative stress. This oxidative stress could be involved in the increase in late apoptosis induced by ziram (10 μmol.L⁻¹) and zinc associated-disulfiram. Concerning gene expression profiles of membrane markers of macrophage polarization, ziram at 10 μmol.L⁻¹ had two opposite effects. It inhibited the gene expression of M2 markers (CD36, CD163) in the same way as the disulfiram-zinc co-treatment. Conversely, ziram induced gene expression of other M2 markers CD209, CD11b, and CD16 in the same way as treatment with zinc alone. Disulfiram-zinc association had no significant effects on these markers. These results taken together show that ziram via zinc modulates macrophages to M2-like anti-inflammatory phenotype which is often associated with various diseases.

Ziram，一种二硫代氨基甲酸锌，在世界范围内广泛用作农业杀菌剂。为了研究齐拉姆诱导的巨噬细胞功能和极化的变化，培养中的人单核细胞衍生的巨噬细胞用 0.01-10 μmol.L ^{-1 的}齐拉姆处理4-24 小时。为了表征锌参与这些变化，我们还确定了双硫仑单独（不含锌的二硫代氨基甲酸盐）或与 ZnSO ₄共同孵育的影响。我们已经证明 0.01 μmol.L ^{-1 的}齐拉姆和双硫仑增加酵母聚糖吞噬作用。相比之下，10 μmol.L ^{-1 的}锆完全抑制了这种吞噬过程、酵母聚糖引发的氧化爆发和 LPS 引发的 TNF-α、IL-1β、IL-6 和 CCL2 的产生。双硫仑仅在与锌 (10 μmol.L ^-1 )结合时对这些巨噬细胞功能具有相同的影响。相比之下，在 10 μmol.L ^-1 ziram 和锌相关联的双硫仑诱导几种抗氧化剂基因 HMOX1、SOD2 和过氧化氢酶的表达，这可能表明氧化应激的诱导。这种氧化应激可能与ziram (10 μmol.L ^-1 ) 和锌相关联的双硫仑诱导的晚期细胞凋亡的增加有关。关于巨噬细胞极化膜标志物的基因表达谱，10 μmol.L ^{-1 的}齐拉姆产生了两个相反的效果。它以与双硫仑-锌联合治疗相同的方式抑制 M2 标志物（CD36、CD163）的基因表达。相反，ziram 以与单独锌处理相同的方式诱导其他 M2 标记物 CD209、CD11b 和 CD16 的基因表达。双硫仑-锌联合对这些标志物没有显着影响。这些结果综合起来表明，ziram 通过锌将巨噬细胞调节为 M2 样抗炎表型，这通常与各种疾病有关。