Azithromycin alleviates systemic lupus erythematosus via the promotion of M2 polarisation in lupus mice.
Azithromycin alleviates systemic lupus erythematosus via the promotion of M2 polarisation in lupus mice.
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阿奇霉素通过促进狼疮小鼠 M2 极化缓解系统性红斑狼疮
DOI：
10.1038/s41420-021-00466-4
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发表时间：
2021-04-16
影响因子：
7
通讯作者：
Xu J
中科院分区：
文献类型：
--
作者：
Wang J;Chen Q;Zhang Z;Wang S;Wang Y;Xiang M;Liang J;Xu J
我们前期的研究表明，阿奇霉素在体外对狼疮条件下的M2巨噬细胞有促进作用，这可能对狼疮的治疗有益。因此，本研究的目的是进一步证实阿奇霉素是否可以驱动狼疮的M2极化并最终在体内缓解系统性红斑狼疮（SLE）。实验中使用淋巴细胞衍生DNA（ALD-DNA）诱导的小鼠（诱导的狼疮模型）和MRL-Faslpr小鼠（自发狼疮模型）。首先，我们通过评估血清抗dsDNA抗体和血清肌酐水平以及肾脏病理来观察狼疮症状。我们发现，这两种小鼠模型显示血清抗dsDNA抗体和肌酐水平升高，肾小球纤维化和细胞浸润增强，基底膜增厚和IgG沉积升高。经阿奇霉素治疗后，上述指标均得到改善，肾损害得到有效逆转。接下来，在脾和肾中评估巨噬细胞极化。在两种小鼠模型中，阿奇霉素治疗后脾脏中的巨噬细胞浸润显著减少，M2巨噬细胞的比例显著升高。此外，白细胞介素（IL）-1、IL-6、肿瘤坏死因子（TNF）-α、诱导型一氧化氮合酶（iNOS）、CD 86、toll样受体（TLR）2和TLR 4的表达显著下调，而转化生长因子（TGF）-β、精氨酸酶-1（Arg-1）、几丁质酶样3（Ym-1）、阿奇霉素治疗后，肾脏中炎症区（Fizz-1）和甘露糖受体（CD 206）的表达显著上调。综上所述，我们的研究结果首次表明阿奇霉素可以通过促进体内M2极化来缓解狼疮。这些发现利用了阿奇霉素的新发现的潜力，阿奇霉素是一种经验证安全性，可负担性和全球可用性的常规药物，这可能是一种通过巨噬细胞调节治疗SLE的新靶向治疗策略。
Our previous study demonstrated that azithromycin could promote alternatively activated (M2) macrophages under lupus conditions in vitro, which might be beneficial for lupus treatment. Thus, the aim of this study was to further confirm whether azithromycin can drive M2 polarisation in lupus and ultimately alleviate systemic lupus erythematosus (SLE) in vivo. Lymphocyte-derived DNA (ALD-DNA)-induced mice (induced lupus model) and MRL-Faslpr mice (spontaneous lupus model) were both used in the experiment. First, we observed symptoms of lupus by assessing the levels of serum anti-dsDNA antibodies and serum creatinine and renal pathology. We found that both murine models showed increased levels of serum anti-dsDNA antibodies and creatinine, enhanced glomerular fibrosis and cell infiltration, basement membrane thickening and elevated IgG deposition. After azithromycin treatment, all these medical indexes were alleviated, and kidney damage was effectively reversed. Next, macrophage polarisation was assessed in the spleen and kidneys. Macrophage infiltration in the spleen was notably decreased after azithromycin treatment in both murine models, with a remarkably elevated proportion of M2 macrophages. In addition, the expression of interleukin (IL)-1, IL-6, tumour necrosis factor (TNF)-α, inducible nitric oxide synthase (iNOS), CD86, toll-like receptor (TLR)2 and TLR4 was extremely downregulated, while the expression of transforming growth factor (TGF)-β, arginase-1 (Arg-1), chitinase-like 3 (Ym-1), found in inflammatory zone (Fizz-1) and mannose receptor (CD206) was significantly upregulated in the kidneys after azithromycin treatment. Taken together, our results indicated for the first time that azithromycin could alleviate lupus by promoting M2 polarisation in vivo. These findings exploited the newly discovered potential of azithromycin, a conventional drug with verified safety, affordability and global availability, which could be a novel treat-to-target strategy for SLE via macrophage modulation.
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影响因子：
4.9
作者：
Kishimoto D;Kirino Y;Tamura M;Takeno M;Kunishita Y;Takase-Minegishi K;Nakano H;Kato I;Nagahama K;Yoshimi R;Igarashi K;Aoki I;Nakajima H
通讯作者：
Nakajima H
影响因子：
4.9
作者：
Feola, David J.;Garvy, Beth A.;Murphy, Brian S.
通讯作者：
Murphy, Brian S.
在小鼠系统性红斑狼疮模型中，IL-6 通过 Treg 抑制方法促进系统性红斑狼疮进展
影响因子：
3.4
作者：
Mao, Xiaoli;Wu, Yunyun;Yin, Zhinan
通讯作者：
Yin, Zhinan
影响因子：
4.4
作者：
Haydar, Dalia;Cory, Theodore J.;Feola, David J.
通讯作者：
Feola, David J.
影响因子：
2.6
作者：
Mohammadi, S.;Saghaeian-Jazi, M.;Memarian, A.
通讯作者：
Memarian, A.