Large-vessel vasculitis
The potential role of leflunomide in inhibiting vascular fibrosis by down-regulating type-II macrophages in Takayasu’s arteritis
X. Cui1, X. Kong2, R. Chen3, L. Ma4, L. Jiang5
- Department of Rheumatology, Zhongshan Hospital, Fudan University, Shanghai, China.
- Department of Rheumatology, Zhongshan Hospital, Fudan University, Shanghai, China.
- Department of Rheumatology, Zhongshan Hospital, Fudan University, Shanghai, China.
- Department of Rheumatology, Zhongshan Hospital, Fudan University, Shanghai, and Evidence-Based Medicine Centre, Fudan University, Shanghai, China.
- Department of Rheumatology, Zhongshan Hospital, Fudan University, Shanghai, and Evidence-Based Medicine Centre, Fudan University, Shanghai, China. zsh-rheum@hotmail.com
CER12477
2020 Vol.38, N°2 ,Suppl.124
PI 0069, PF 0078
Large-vessel vasculitis
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PMID: 31969231 [PubMed]
Received: 02/06/2019
Accepted : 18/11/2019
In Press: 14/01/2020
Published: 21/05/2020
Abstract
OBJECTIVES:
Inflammatory fibrosis of aortic lesions promoted by type II macrophages (M2) is one of the most serious incidents in Takayasu’s arteritis (TAK), and the currently available therapies can not effectively block the inflammatory fibrosis. Here we explored whether leflunomide (LEF) could improve the fibrosis by down-regulating M2 in TAK.
METHODS:
Peripheral blood mono-nuclear cells (PBMCs) from 16 TAK patients were treated by leflunomide, and the ratio of M1/M2 macrophages and apoptosis of M2 were detected by flow cytometry. Supernatant levels of cytokines and chemokines secreted by M2 were measured by ELISAs. mRNA expression of profibrotic factors in M2 were analysed by real time PCR. Western blotting was used to analyse the activation of signal transducer activator of transcription (STAT)-6.
RESULTS:
LEF could inhibit M2 polarisation by curtailing STAT6 phosphorylation. LEF could also promote apoptosis of M2 and reduce the release of M2-derived CCL22 as well as the expression of profibrotic cytokines including CCL22 and TGF-β in M2.
CONCLUSIONS:
LEF could potentially reduce vascular fibrosis by down-regulating the number and function of M2, which, eventually, could alleviate inflammatory fibrosis of aortic lesions in TAK patients.
