Liu Enna, Li Zheng, Zhang Yan, Chen Kuisheng
Department of Tumor Pathology, Luohe Medical College, Henan, China.
Iran J Immunol. 2019 Sep;16(3):190-199. doi: 10.22034/IJI.2019.80270.
Macrophage polarization plays a critical role in determining the inflammatory states. Hepcidin is a key negative regulator of iron homeostasis and functions. Although hepcidin has been shown to affect ferroportin expression in macrophages, whether it affects macrophage polarization is still largely unknown.
To address whether hepcidin induces macrophage polarization.
The expression of iNOS and CD206, and the ratio of IFN-γ vs IL-4 in THP-1 derived macrophages upon hepcidin stimulation were evaluated. Further detected was the percentage of CD16+ M1, CD23+ M1, CD10+ M2 and CCL22+ M2 cells in monocyte derived macrophages.
M1 associated molecules were increased in hepcidin-treated cells, yet M2 associated molecules were increased when hepcidin was neutralized. Concomitantly, we observed a significant increase in IRF3 phosphorylation in hepcidin-stimulated cells. However, STAT6 phosphorylation with hepcidin was neutralized.
Hepcidin is able to induce macrophage polarization towards M1 type, and might be utilized as a potential M1 macrophage agonist in clinical practice.
巨噬细胞极化在决定炎症状态中起关键作用。铁调素是铁稳态和功能的关键负调节因子。尽管已表明铁调素会影响巨噬细胞中铁转运蛋白的表达，但它是否影响巨噬细胞极化仍很大程度上未知。
探讨铁调素是否诱导巨噬细胞极化。
评估铁调素刺激后THP-1来源的巨噬细胞中诱导型一氧化氮合酶（iNOS）和CD206的表达，以及IFN-γ与IL-4的比值。进一步检测单核细胞来源的巨噬细胞中CD16+ M1、CD23+ M1、CD10+ M2和CCL22+ M2细胞的百分比。
铁调素处理的细胞中M1相关分子增加，但铁调素被中和时M2相关分子增加。同时，我们观察到铁调素刺激的细胞中IRF3磷酸化显著增加。然而，铁调素被中和时STAT6磷酸化。
铁调素能够诱导巨噬细胞向M1型极化，在临床实践中可能用作潜在的M1巨噬细胞激动剂。
