The role of classical and alternative macrophages in the immunopathogenesis of herpes simplex virus-induced inflammation in a mouse model
The role of classical and alternative macrophages in the immunopathogenesis of herpes simplex virus-induced inflammation in a mouse model
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DOI：
10.1016/j.jdermsci.2013.11.001
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发表时间：
2014-03-01
影响因子：
4.6
通讯作者：
Sohn, Seonghyang
中科院分区：
文献类型：
--
作者：
Anower, A. K. M. M.;Shim, Ju A.;Sohn, Seonghyang
背景：白吉特病（BD）发展过程中发生炎症变化的确切机制仍不清楚。目的：我们研究了单纯疱疹病毒（HSV）诱导的BD小鼠模型中经典（M1）和替代（M2）巨噬细胞激活的作用。方法：通过分别分析表面标记CD16/32和CD23作为M1和M2标记，计算经典与替代激活巨噬细胞比率（Ml/M2比率），通过流式细胞术。通过逆转录聚合酶链反应分析干扰素（IFN）-γ和白细胞介素（IL）-6作为M1标记以及精氨酸酶-1、FIZZ-1和MHC-II作为M2标记的mRNA表达。通过酶联免疫吸附测定法评估细胞因子水平。结果：与无症状BD正常小鼠和正常健康小鼠相比，BD小鼠的M1表型上调，并且观察到M1/M2比率增加。与rIL-4 (0.83 +/- 0.20) 相比，重组(r)IFN-gamma 显着增加了M1/M2 比率(1.74 +/- 0.42)。与rIFN-γ(2.1+/-2.3)治疗组相比，用rIL-4治疗的BD小鼠表现出降低的Ml/M2比率(1.2+/-0.3)，并且还表现出改善的BD症状，伴随着IL-17和IL-6的下调以及IL-4的上调。结论：因此，巨噬细胞表型的调节可能是未来治疗BD的有效治疗方法。 (C) 2013 年日本皮肤病研究学会。由爱思唯尔爱尔兰有限公司出版。保留所有权利。
Background: The exact mechanism of the inflammatory changes occurring during the development of Behget's disease (BD) remains unclear.Objective: We investigated the role of classical (M1) and alternative (M2) activation of macrophages in a herpes simplex virus (HSV)-induced BD mouse model.Methods: The classical vs. alternative activated macrophage ratio (Ml/M2 ratio) was calculated by analyzing the surface markers CD16/32 and CD23 as M1 and M2 markers, respectively, by flow cytometry. mRNA expression of interferon (IFN)-gamma and interleukin (IL)-6 as M1 and arginase-1, FIZZ-1, and MHC-II as M2 markers were analyzed by reverse transcription-polymerase chain reaction. Cytokine levels were assessed by enzyme-linked immunosorbent assay.Results: The M1 phenotype was upregulated in BD mice, and an increased M1/M2 ratio was observed compared to that in asymptomatic BD normal and normal healthy mice. Recombinant (r)IFN-gamma significantly increased the M1/M2 ratio (1.74 +/- 0.42) compared with that of rIL-4 (0.83 +/- 0.20). BD mice treated with rIL-4 showed a decreased Ml/M2 ratio (1.2 +/- 0.3) compared to that of the rIFN-gamma- (2.1 +/- 2.3) treated group and also showed ameliorated BD symptoms accompanied by downregulation of IL-17 and IL-6 and up-regulation of IL-4.Conclusion: Therefore, modulation of macrophage phenotypes could be an effective therapeutic approach for treating BD in the future. (C) 2013 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.