CP-25 alleviates antigen-induced experimental Sjögren's syndrome in mice by inhibiting JAK1-STAT1/2-CXCL13 signaling and interfering with B-cell migration

Wu, Huaxun; Chen, Xiaoyun; Gu, Fei; Zhang, Pengying; Xu, Shouping; Liu, Qi; Zhang, Qiaolin; Wang, Xinming; Wang, Chun; Körner, Heinrich; Wei, Wei

doi:10.1038/s41374-020-0453-0

Cited by 14 publications

(8 citation statements)

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“…Therefore, there is an urgent need to develop new agents for treating IBD that are effective and easily available and present fewer adverse reactions. Previous studies have demonstrated that CP‐25 has anti‐inflammatory and immune regulatory activities in animal models of inflammatory autoimmune disease 13,14 . However, the therapeutic effects of CP‐25 against colitis and its regulatory mechanism have been uncertain.…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies have demonstrated that CP-25 has anti-inflammatory and immune regulatory activities in animal models of inflammatory autoimmune disease. 13,14 However, the therapeutic effects of CP-25 against colitis and its regulatory mechanism have been uncertain.…”

Section: Discussionmentioning

confidence: 99%

“…Paeoniflorin‐6′‐ O ‐benzene sulfonate (CP‐25) is a novel active monomeric anti‐inflammatory and immunomodulatory agent produced by chemical structural modifications of paeoniflorin. CP‐25 has proved effective in improving the clinical manifestations of arthritis in animal models and experimental Sjögren's syndrome mice 13,14 . In animal models of autoimmune arthritis, CP‐25 modulates the production of cytokines by downregulating M1 macrophage activation and upregulating M2 macrophage activation to alleviate inflammation.…”

Section: Introductionmentioning

confidence: 99%

“…CP-25 has proved effective in improving the clinical manifestations of arthritis in animal models and experimental Sjögren's syndrome mice. 13,14 In animal models of autoimmune arthritis, CP-25 modulates the production of cytokines by downregulating M1 macrophage activation and upregulating M2 macrophage activation to alleviate inflammation. This demonstrates the immunotherapeutic effects of CP-25 in restoring the abnormal polarization of macrophages.…”

Section: Introductionmentioning

confidence: 99%

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CP‐25 exerts therapeutic effects in mice with dextran sodium sulfate‐induced colitis by inhibiting GRK2 translocation to downregulate the TLR4‐NF‐κB‐NLRP3 inflammasome signaling pathway in macrophages

et al. 2021

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Deficiency of G protein‐coupled receptor kinase 2 (GRK2) was found to protect mice from dextran sulfate sodium (DSS)‐induced colitis. Paeoniflorin‐6′‐O‐benzene sulfonate (CP‐25) has been shown to exert anti‐inflammatory immune regulatory effects in animal models of inflammatory autoimmune disease. This study aimed to investigate the of GRK2 in the pathogenesis of ulcerative colitis (UC) and its effects on macrophage polarization, macrophage subtype regulation of intestinal barrier function, and therapeutic effects of CP‐25 in mice with DSS‐induced colitis. We found imbalanced macrophage polarization, intestinal barrier dysfunction, and abnormal activation of GRK2 and TLR4‐NF‐κB‐NLRP3 inflammasome signaling pathway in the colonic mucosa of patients with UC. CP‐25, restored the damaged intestinal barrier function by inhibiting the transmembrane region of GRK2 in macrophages stimulated by lipopolysaccharides. CP‐25 exerted therapeutic effects by ameliorating clinical manifestation, regulating macrophage polarization, and restoring abnormally activated TLR4‐NF‐κB‐NLRP3 inflammasome signaling pathway by inhibiting GRK2. These data suggest the pathogenesis of UC may be related to the imbalance of macrophage polarization, which leads to abnormal activation of TLR4‐NF‐κB‐NLRP3 inflammasome signaling pathway mediated by GRK2 and destruction of the intestinal mucosal barrier. CP‐25 confers therapeutic effects on colitis by inhibiting GRK2 translocation to induce the downregulation of TLR4‐NF‐κB‐NLRP3 inflammasome signaling in macrophages.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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CP‐25 exerts therapeutic effects in mice with dextran sodium sulfate‐induced colitis by inhibiting GRK2 translocation to downregulate the TLR4‐NF‐κB‐NLRP3 inflammasome signaling pathway in macrophages

et al. 2021

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“…In this ESS model, Th17 cells also play a critical role in disease pathogenesis [11]. Hence, several studies have been carried out to investigate potential therapeutic drugs and molecular mechanisms against SS [31][32][33].…”

Section: Discussionmentioning

confidence: 99%

Effect of the Chinese Herbal Medicine SS-1 on a Sjögren’s Syndrome-Like Disease in Mice

Lin

Panny

et al. 2021

Life

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Sjögren’s syndrome (SS) is an inflammatory autoimmune disease primarily affecting the exocrine glands; it has a major impact on patients’ lives. The Chinese herbal formula SS-1 is composed of Gan Lu Yin, Sang Ju Yin, and Xuefu Zhuyu decoction, which exerts anti-inflammatory, immunomodulatory, and antifibrotic effects. Our previous study demonstrated that SS-1 alleviates clinical SS. This study aimed to evaluate the efficacy and mechanism of the Chinese herbal formula SS-1 for salivary gland protein-induced experimental Sjögren’s syndrome (ESS). These results showed that ESS treatment with the Chinese herbal formula SS-1 (1500 mg/kg) significantly alleviated the severity of ESS. We found that SS-1 substantially improved saliva flow rates in SS mice and ameliorated lymphocytic infiltrations in submandibular glands. In addition, salivary gland protein-induced SS in mice treated with SS-1 significantly lowered proinflammatory cytokines (including IFN-γ, IL-6, and IL-17A) in mouse salivary glands and decreased serum anti-M3R autoantibody levels. In addition, we found that CD4+ T cells isolated from SS-1-treated SS mice significantly reduced the percentages of IFN-γ-producing CD4+ T cells (Th1) and IL-17A-producing CD4+ T cells (Th17). Our data show that SS-1 alleviates ESS through anti-inflammatory and immunomodulatory effects, which provides new insight into the clinical treatment of SS.

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PRMT5 participates in B cell overactivation in patients with primary Sjogren's syndrome (pSS) through RSAD2‐mediated NF‐κB signaling

Zhu,

Zheng,

Zhou

et al. 2023

Immunity Inflam & Disease

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ObjectiveThere are new evidences that protein arginine methyltransferase 5 (PRMT5) is widely involved in the progression of various diseases, but its effect is unclear on Primary Sjogren's syndrome (pSS). The main purpose of this study is to explore the regulatory effect of PRMT5 on pSS and its potential mechanisms.MethodsCD40L treated CD19 + B cells to construct a cell model of pSS. CCK‐8 assay and Annexin V‐FITC/PI kits were used to measure cell proliferation and apoptosis. ELISA assay was used to determine the contents of IL‐6 and TNF‐α in CD19 + B cells. And commercial kits were used to detect the levels of immunoglobins (IgG, IgM, and IgA) in CD40L‐treated CD19 + B cells. And successfully constructed a pSS mouse model.ResultsThe results revealed an increase in the expression of PRMT5 in CD19 + B cells from patients with pSS. After CD40L treatment, the knockdown of PRMT5 prominently decreased cell viability, the production level of immunoglobulins (IgG, IgM, and IgA), and the content of IL‐10, increased the content of IL‐6 and IL‐8, and promoted the apoptosis of pSS CD19 + B cells. Mechanistically, PRMT5 negatively regulated the RSAD2 and nuclear factor kappa‐B (NF‐κB) signaling pathway. Furthermore, overexpression of RSAD2 and p65 significantly rescued the effect of PRMT5 knockdown on proliferation, immunoglobin production and secreting cytokines in CD40L‐treated CD19 + B cells. More importantly, inhibition of PRMT5 significantly inhibited the symptoms of pSS mice.ConclusionsLow‐expression of PRMT5 through inactivation of RSAD2/NF‐κB signalling pathway alleviates the hyperactivity of B cells, which may provide theoretical basis and potential therapeutic targets for clinical treatment of pSS.

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CP-25 alleviates antigen-induced experimental Sjögren's syndrome in mice by inhibiting JAK1-STAT1/2-CXCL13 signaling and interfering with B-cell migration

Cited by 14 publications

References 46 publications

CP‐25 exerts therapeutic effects in mice with dextran sodium sulfate‐induced colitis by inhibiting GRK2 translocation to downregulate the TLR4‐NF‐κB‐NLRP3 inflammasome signaling pathway in macrophages

CP‐25 exerts therapeutic effects in mice with dextran sodium sulfate‐induced colitis by inhibiting GRK2 translocation to downregulate the TLR4‐NF‐κB‐NLRP3 inflammasome signaling pathway in macrophages

Effect of the Chinese Herbal Medicine SS-1 on a Sjögren’s Syndrome-Like Disease in Mice

PRMT5 participates in B cell overactivation in patients with primary Sjogren's syndrome (pSS) through RSAD2‐mediated NF‐κB signaling

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