Traditionally, the treatment of inflammatory conditions has focused on the inhibition of inflammatory mediator production; however, many conditions are refractory to this classical approach. Recently, an alternative has been presented by researchers to solve this problem: The immunomodulation of cells closely related to inflammation. Hence, macrophages, a critical key in both innate and acquired immunity, have been presented as an alternative target for the development of new medicines. In this work, we tested the fluorophenyl-imidazole for its anti-inflammatory activity and possible immunomodulatory effect on RAW 264.7 macrophages. We also evaluated the anti-inflammatory effect of the compound, and the macrophage repolarization to M2 was confirmed by the ability of the compound to reduce the M1 markers TNF-α, IL-6, MCP-1, IL-12p70, IFN-γ, and TLR4, the high levels of p65 phosphorylated, iNOS and COX-2 mRNA expression, and the fact that the compound was not able to induce the production of M1 markers when used in macrophages without lipopolysaccharide (LPS) stimulation. Moreover, fluorophenyl-imidazole had the ability to increase the M2 markers IL-4, IL-13, CD206, apoptosis and phagocytosis levels, arginase-1, and FIZZ-1 mRNA expression before LPS stimulation. Similarly, it was also able to induce the production of these same M2 markers in macrophages without being induced with LPS. These results reinforce the affirmation that the fluorophenyl-imidazole has an important anti-inflammatory effect and demonstrates that this effect is due to immunomodulatory activity, having the ability to trigger a repolarization of macrophages from M1 to M2a. These facts suggest that this molecule could be used as an alternative scaffold for the development of a new medicine to treat inflammatory conditions, where the anti-inflammatory and proregenerative properties of M2a macrophages are desired.

中文翻译：

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巨噬细胞平衡 (M1/M2) 的干扰：氟苯基取代咪唑抗炎作用的作用机制


传统上，炎症性疾病的治疗重点是抑制炎症介质的产生。然而，许多条件对于这种经典方法来说是难以解决的。最近，研究人员提出了一种替代方案来解决这个问题：与炎症密切相关的细胞的免疫调节。因此，巨噬细胞作为先天性和获得性免疫的关键，已被视为新药开发的替代靶点。在这项工作中，我们测试了氟苯基咪唑的抗炎活性以及对 RAW 264.7 巨噬细胞可能的免疫调节作用。我们还评估了该化合物的抗炎作用，通过该化合物降低 M1 标志物 TNF- α 、IL-6、MCP-1、IL-12p70、IFN- γ的能力证实了巨噬细胞复极化至 M2和 TLR4、高水平的 p65 磷酸化、iNOS 和 COX-2 mRNA 表达，以及该化合物在没有脂多糖 (LPS) 刺激的情况下用于巨噬细胞时无法诱导 M1 标记物的产生。此外，氟苯基咪唑能够在 LPS 刺激前增加 M2 标记物 IL-4、IL-13、CD206、细胞凋亡和吞噬水平、精氨酸酶 1 和 FIZZ-1 mRNA 表达。同样，它也能够诱导巨噬细胞产生这些相同的 M2 标记物，而无需用 LPS 诱导。这些结果进一步证实了氟苯基咪唑具有重要的抗炎作用，并证明这种作用是由于免疫调节活性所致，能够触发巨噬细胞从 M1 复极化为 M2a。 这些事实表明，该分子可以用作开发治疗炎症疾病的新药的替代支架，其中需要 M2a 巨噬细胞的抗炎和再生特性。