Department of Dermatology, Kagawa University, Kagawa, Japan.
Department of Medicine, Section of Dermatology, University of Chicago, Chicago, USA.
Sci Rep. 2017 Sep 29;7(1):12473. doi: 10.1038/s41598-017-12756-y.
Macrophages are central to inflammatory response and become polarized towards the M1 or M2 states upon activation by immunostimulants. In this study, we investigated the effects of lipopolysaccharides (LPS) and interleukin (IL)-17A on the activation of macrophages in in vivo mouse skin. We examined whether macrophages are activated in the skin of imiquimod (IMQ)-treated mice, a model for IL-17A-induced psoriasis-like skin inflammation, and flaky-tail (Flg ) mice, a model for IL-17A-induced chronic atopic dermatitis-like skin inflammation. LPS and IL-17A independently increased the expression levels of iNOS, CX3CR1, CD206, phospho-STAT1 and phospho-STAT3 proteins in the skin of B6 mice, and the effects of LPS was not altered by IL-17A. The expression levels of these proteins were increased in the skin of IMQ-treated and Flg mice. IL-17A neutralization increased the expressions of iNOS and phospho-STAT1 in the IMQ-treated skin, but it decreased the expressions of CD206 and phospho-STAT3 proteins in the skin of Flg mice, suggesting that macrophages to change from the M2 to the M1 state in the skin of these mice. These results suggest that IL-17A is involved in the activation of macrophages that are in the process of adopting the heterogeneous profiles of both the M1 and M2 states.
巨噬细胞是炎症反应的核心，在受到免疫刺激剂激活后，会向 M1 或 M2 状态极化。在这项研究中，我们研究了脂多糖（LPS）和白细胞介素（IL）-17A 对体内小鼠皮肤中巨噬细胞激活的影响。我们检查了在咪喹莫特（IMQ）处理的小鼠皮肤中是否激活了巨噬细胞，IMQ 是一种诱导 IL-17A 引起的银屑病样皮肤炎症的模型，以及 Flg 小鼠，这是一种诱导 IL-17A 引起的慢性特应性皮炎样皮肤炎症的模型。LPS 和 IL-17A 独立地增加了 B6 小鼠皮肤中 iNOS、CX3CR1、CD206、磷酸化 STAT1 和磷酸化 STAT3 蛋白的表达水平，而 IL-17A 对 LPS 的作用没有改变。这些蛋白质的表达水平在 IMQ 处理和 Flg 小鼠的皮肤中增加。IL-17A 中和增加了 IMQ 处理皮肤中 iNOS 和磷酸化 STAT1 的表达，但降低了 Flg 小鼠皮肤中 CD206 和磷酸化 STAT3 蛋白的表达，表明这些小鼠皮肤中的巨噬细胞从 M2 状态向 M1 状态转变。这些结果表明，IL-17A 参与了正在经历 M1 和 M2 状态异质特征的巨噬细胞的激活。
