The mechanism of Langchuangding in treatment of systemic lupus erythematosus via modulating TLR7-IRF7-IFNα pathway

Meijiao Wang; Yiyang Zhang; Yingqi Zhai; Haichang Li; Zhijun Xie; Chengping Wen

Heliyon (Mar 2024)

The mechanism of Langchuangding in treatment of systemic lupus erythematosus via modulating TLR7-IRF7-IFNα pathway

Meijiao Wang,
Yiyang Zhang,
Yingqi Zhai,
Haichang Li,
Zhijun Xie,
Chengping Wen

Affiliations

Meijiao Wang: Research Institute of Chinese Medicine Clinical Foundation and Immunology, School of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, 310053, Zhejiang, China
Yiyang Zhang: Research Institute of Chinese Medicine Clinical Foundation and Immunology, School of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, 310053, Zhejiang, China
Yingqi Zhai: Research Institute of Chinese Medicine Clinical Foundation and Immunology, School of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, 310053, Zhejiang, China
Haichang Li: Research Institute of Chinese Medicine Clinical Foundation and Immunology, School of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, 310053, Zhejiang, China
Zhijun Xie: Corresponding author.; Research Institute of Chinese Medicine Clinical Foundation and Immunology, School of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, 310053, Zhejiang, China
Chengping Wen: Corresponding author.; Research Institute of Chinese Medicine Clinical Foundation and Immunology, School of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, 310053, Zhejiang, China

Journal volume & issue: Vol. 10, no. 5
p. e26022

Abstract

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Object: Systemic lupus erythematosus (SLE) is a complex autoimmune disease characterized by aberrant activity of the immune system. Plasmacytoid dendritic cells (pDCs) which the main producer of activated type I interferon, are related to SLE disease activity. To investigate the mechanism of Langchuangding (LCD) improving SLE based on TLR7-IRF7-IFNα pathway. Methods: SLE patients were randomly divided into Chinese medicine combined with western medicine (CWM) group and western medicine (WM) group, to observe the effect of LCD. The percent of pDCs in peripheral blood of SLE patients were detected by flow cytometry, and the influence of LCD on gene expression in SLE patients were detected by gene microarray. Mouse bone marrow cells were differentiated into dendritic like cells (DLC), then divided into Blank, immune complex (IC), LCD and dexamethasone (DXM) group. Employed RT-qPCR to detect MyD88, and IRF7 mRNA, and western blotting to determinate TLR7, MyD88, and p-IRF7 proteins. The IFNα in SLE patients were detected by enzyme-linked immunosorbent assay (ELISA). Employ dual luciferase to observe the interferon stimulated response element (ISRE) gene. Results: pDCs in WM group was higher than that of CWM group. The plasma IFNα in CWM group was significantly lower than that in WM group. The gene microarray showed that the gene expression of IFNα related signaling pathway in peripheral blood mononuclear cell (PBMC) and genes related to activation and proliferation of immune cells were down-regulated after LCD treatment. The DLCs MyD88, and IRF7 mRNA were down-regulated, TLR7, MyD88, and p-IRF7 proteins were significantly reduced, and the supernatant IFNα was significantly decreased in LCD group. LCD were mildly inhibited activation of ISRE in 293T cells. Conclusions: In certain degree, LCD is beneficial to SLE patients. LCD therapy SLE may be through TLR7 signaling pathway, and IRF7 may be a promising therapeutic target for the treatment of SLE.

Published in Heliyon

ISSN: 2405-8440 (Online)
Publisher: Elsevier
Country of publisher: United Kingdom
LCC subjects: Science: Science (General); Social Sciences: Social sciences (General)
Website: https://www.cell.com/heliyon/home

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