Jieduquyuziyin Prescription Suppresses Inflammatory Activity of MRL/lpr Mice and Their Bone Marrow-Derived Macrophages via Inhibiting Expression of IRAK1-NF-κB Signaling Pathway.

Lina Ji,Yongsheng Fan,Jie Bao,Xuemin Fan,Rongqun Li,Aiwen Zhuang,Danqing Fu,Sixiang Chen,Xiaoli Hou

doi:10.3389/fphar.2020.01049

Abstract

Jieduquyuziyin prescription (JP) has been used to treat systemic lupus erythematosus (SLE). Although the effectiveness of JP in the treatment of SLE has been clinically proven, the underlying mechanisms have yet to be completely understood. We observed the therapeutic actions of JP in MRL/lpr mice and their bone marrow-derived macrophages (BMDMs) and the potential mechanism of their inhibition of inflammatory activity. To estimate the effect of JP on suppressing inflammatory activity, BMDMs of MRL/lpr and MRL/MP mice were treated with JP-treated serum, and MRL/lpr mice were treated by JP for 8 weeks. Among them, JP and its treated serum were subjected to quality control, and BMDMs were separated and identified. The results showed that in the JP group of BMDMs stimulated by Lipopolysaccharide (LPS) in MRL/lpr mice, the secretion of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) reduced, and the expressions of Interleukin-1 receptor-associated kinase 1 (IRAK1) and its downstream nuclear factor κB (NF-κB) pathway decreased. Meanwhile, the alleviation of renal pathological damage, the decrease of urinary protein and serum anti-dsDNA contents, the inhibition of TNF-α level, and then the suppression of the IRAK1-NF-κB inflammatory signaling in the spleen and kidney, confirmed that the therapeutic effect of JP. These results demonstrated that JP could inhibit the inflammatory activity of MRL/lpr mice and their BMDMs by suppressing the activation of IRAK1-NF-κB signaling and was supposed to be a good choice for the treatment of SLE.

Highlights

Systemic lupus erythematosus (SLE) is the most severe type of lupus erythematosus, and it is an autoimmune-mediated chronic diffuse connective tissue disease involving multiple organs in the body, which is characterized by immune inflammation (Muñoz et al, 2011; Casciato et al, 2018)
Compared with bone marrow-derived macrophages (BMDMs) in MRL/MP, Jieduquyuziyin prescription (JP) significantly reduced the activation of Interleukin-1 receptor-associated kinase 1 (IRAK1) and its downstream inflammatory signals in MRL/lpr mice
We previously investigated the effects of JP on the level of methylation in T lymphocytes to explore the pathogenesis of SLE (Li et al, 2018b)

Summary

Introduction

Systemic lupus erythematosus (SLE) is the most severe type of lupus erythematosus, and it is an autoimmune-mediated chronic diffuse connective tissue disease involving multiple organs in the body, which is characterized by immune inflammation (Muñoz et al, 2011; Casciato et al, 2018). The current treatments for SLE include glucocorticoids and immunosuppressant agents. These conventional treatments can relieve certain symptoms and temporarily prevent disease progression, they have limited therapeutic effects (Li et al, 2017). In China, some clinical Chinese medicine formulas for SLE which include Jieduquyuziyin prescription (JP) are generally accepted by many people because of the due effect and minimal adverse reactions (Fan et al, 2005; Fan, 2019). JP has been exclusively and validly applied in the treatment of SLE for more than a decade in the Chinese Traditional Medicine Hospital of Zhejiang Province, China. JP has been proved to be efficacious in the treatment of SLE, little is known about the exact mechanism and target of drug, so it is necessary to find new drug targets for SLE

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Conclusion