Department of Cardiology, Affiliated Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430077, China.
Department of Anatomy, School of Basic Medical Sciences, Hubei University of Chinese Medicine, Wuhan 430065, China.
Int Immunopharmacol. 2019 Jan;66:82-90. doi: 10.1016/j.intimp.2018.11.009. Epub 2018 Nov 13.
Berberine (BBR) possesses many pharmacological characteristics including anti-inflammation, anti-allergy, anti-angiogenesis and anti-tumor. However, the effects and mechanisms of BBR on IL-33-induced mast cell inflammatory responses are kept unknown. To investigate these, rat peritoneal mast cells (RPMCs) were isolated from the peritoneal cavity and cultured with BBR treatment in combination IL-33 stimulation. Firstly, cytotoxic effect of BBR on RPMCs was detected by MTT assay. Then, IL-33-induced cytokine production and the expression of ST2 receptor, were evaluated by ELISA and real-time PCR, respectively. In addition, NF-κB and MAPK signaling involved in IL-33-mediated mast cell activation were assessed by Western blot, which also was confirmed using the signal transduction inhibitors. Simultaneously, the effect of BBR on IL-33-activated enhancement of IgE-mediated mast cell responses was analyzed. Lastly, SD rats were used to explore the effect of BBR on IL-33-induced inflammation in vivo. BBR treatment significantly reduced IL-33-stimulated cytokine production in RPMCs, such as IL-6, TNF-α, IL-13 and MCP-1, but had little effect in ST2 expression. BBR modulated IL-33 signaling via suppressing IL-33-induced NF-ΚB transcription and p38 phosphorylation, but not ERK and JNK. Additionally, BBR also hampered the combined effects of IL-33 and IgE-mediated mast cell activation. Decreased cytokine production followed BBR treatment in vitro was consistent with that in vivo, where BBR injection i.p. into rats obviously inhibited IL-33-induced plasma cytokine levels. These findings demonstrated that BBR suppressed IL-33-mediated inflammation in mast cells by inactivating NF-κB and p38 signaling, suggesting its potential application for the treatment of allergic inflammation.
小檗碱（BBR）具有许多药理学特性，包括抗炎、抗过敏、抗血管生成和抗肿瘤。然而，BBR 对 IL-33 诱导的肥大细胞炎症反应的影响和机制尚不清楚。为了研究这些问题，我们从腹腔中分离出大鼠腹膜肥大细胞（RPMC），并用 BBR 处理联合 IL-33 刺激进行培养。首先，通过 MTT 测定法检测 BBR 对 RPMC 的细胞毒性作用。然后，通过 ELISA 和实时 PCR 分别评估 IL-33 诱导的细胞因子产生和 ST2 受体的表达。此外，通过 Western blot 评估了 NF-κB 和 MAPK 信号通路在 IL-33 介导的肥大细胞激活中的作用，该信号通路也通过使用信号转导抑制剂进行了验证。同时，分析了 BBR 对 IL-33 激活增强 IgE 介导的肥大细胞反应的影响。最后，使用 SD 大鼠在体内研究 BBR 对 IL-33 诱导的炎症的作用。BBR 处理显著降低了 RPMC 中 IL-33 刺激的细胞因子产生，如 IL-6、TNF-α、IL-13 和 MCP-1，但对 ST2 表达影响不大。BBR 通过抑制 IL-33 诱导的 NF-ΚB 转录和 p38 磷酸化来调节 IL-33 信号，但不影响 ERK 和 JNK。此外，BBR 还阻碍了 IL-33 和 IgE 介导的肥大细胞激活的联合作用。体外 BBR 处理后细胞因子产生减少与体内情况一致，其中腹腔注射 BBR 明显抑制了大鼠 IL-33 诱导的血浆细胞因子水平。这些发现表明，BBR 通过失活 NF-κB 和 p38 信号来抑制 IL-33 介导的肥大细胞炎症，提示其在治疗过敏炎症方面的潜在应用。
