Paeoniflorin Inhibits LPS-Induced Activation of Splenic CD4+ T Lymphocytes and Relieves Pathological Symptoms in MRL/lpr Mice by Suppressing IRAK1 Signaling

Lina Ji; Shenglong Wang; Shan Wu; Jie Bao; Guanqun Xie; Yan Zhang; Liping Xu; Na Lin; Jian Wang; Yongsheng Fan; Danqing Fu; Qiaoding Dai

doi:10.1155/2022/5161890

Paeoniflorin Inhibits LPS-Induced Activation of Splenic CD4⁺ T Lymphocytes and Relieves Pathological Symptoms in MRL/lpr Mice by Suppressing IRAK1 Signaling

Evid Based Complement Alternat Med. 2022 Nov 23:2022:5161890. doi: 10.1155/2022/5161890. eCollection 2022.

Authors

Lina Ji¹, Shenglong Wang², Shan Wu³, Jie Bao⁴, Guanqun Xie⁴, Yan Zhang¹, Liping Xu¹, Na Lin¹, Jian Wang¹, Yongsheng Fan⁴, Danqing Fu⁴, Qiaoding Dai¹

Affiliations

¹ The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310003, Zhejiang Province, China.
² The First School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou 310053, Zhejiang Province, China.
³ The First Affiliated Hospital of Hangzhou Normal University, Hangzhou 310015, Zhejiang Province, China.
⁴ School of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou 310053, Zhejiang Province, China.

Abstract

Interleukin-1receptor-associated kinase 1 (IRAK1) plays a critical role in systemic lupus erythematosus (SLE). It was reported that SLE was associated with an inflammatory response mediated by defective immune tolerance, including overproduction of autoantibodies, chronic inflammation, and organ damage. Previous reports stated paeoniflorin (PF) had an immunosuppressive effect. The purpose of this study was to determine the anti-inflammatory effect of PF in SLE and its underlying mechanisms. Followed by induced with lipopolysaccharide (LPS), the splenocytes and the isolated CD4⁺ T lymphocytes of MRL/lpr mice were divided into three groups: control group, LPS group, and LPS + PF group, respectively. MRL/MP mice were used as the control group (treated with distilled water). The MRL/lpr mice were randomly divided into three groups: the model group (treated with distilled water), the prednisone group, and the PF group. The MRL/lpr mice were treated with prednisone acetate (5 mg/kg) and PF (25, 50, and 75 mg/kg) for eight weeks. Subsequently, ELISA, qRT-PCR, western blotting, HE, and Masson staining were performed to detect various indicators. The results of Cell Counting Kit-8 (CCK-8) showed that 10 μg/mL of LPS had the optimum effect on cell viability, and 50 μmol/L of PF had no obvious cytotoxicity to LPS-treated cells. PF reduced the expression level of IRAK1-nuclearfactor-κB (NF-κB) and its downstream inflammatory cytokines in the splenocytes and CD4⁺ T lymphocytes of MRL/lpr mice stimulated by LPS, especially in the latter. The serum antibody contents in the PF group mice were reduced, and the kidney damage was also alleviated accordingly. Moreover, the IRAK1/inhibitor of the nuclear factor-κB kinase (IKK)/NF-κB inhibitor (IκB)/NF-κB pathways was found to be involved in the anti-inflammation effect of PF in the kidney and spleen. In conclusion, it is thought that PF may have the potential to be used as a therapeutic agent to reduce the inflammatory activity of SLE. Inhibition of the IRAK1-NF-κB pathway may help formulate novel therapeutic tactics for SLE.