Azithromycin alleviates systemic lupus erythematosus via the promotion of M2 polarisation in lupus mice
Autor: | Jun Liang, Shangshang Wang, Yilun Wang, Jinhua Xu, Jie Wang, Zhixiong Zhang, Mengmeng Xiang, Qian Chen |
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Jazyk: | angličtina |
Rok vydání: | 2021 |
Předmět: |
0301 basic medicine
Cancer Research Immunology Spleen Azithromycin Article 03 medical and health sciences Cellular and Molecular Neuroscience 0302 clinical medicine Fibrosis immune system diseases medicine skin and connective tissue diseases Immunological disorders RC254-282 030203 arthritis & rheumatology Kidney Systemic lupus erythematosus QH573-671 business.industry Drug discovery Interleukin Neoplasms. Tumors. Oncology. Including cancer and carcinogens Cell Biology medicine.disease 030104 developmental biology medicine.anatomical_structure TLR4 Tumor necrosis factor alpha business Cytology medicine.drug |
Zdroj: | Cell Death Discovery, Vol 7, Iss 1, Pp 1-12 (2021) Cell Death Discovery |
ISSN: | 2058-7716 |
Popis: | 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. |
Databáze: | OpenAIRE |
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