RNA结合蛋白KSRP可降低模型小鼠哮喘样特征
2025/06/27
摘要
背景：哮喘是一种慢性炎症性疾病，其特征是细胞因子表达失调。RNA结合蛋白KSRP可降低几种促炎介质表达。
目的：因此，本研究旨在研究KSRP可调节卵清蛋白（OVA）诱导过敏性哮喘模型C57BL/6 KSRP缺陷小鼠（KSRP-/-）体内Th2相关免疫反应。
方法：本研究通过测定气道高反应性（AHR）、肺组织结构变化和OVA特异性抗体水平以评估OVA致敏野生型或KSRP-/-小鼠的哮喘严重程度。通过细胞计数珠阵列（CBA）分析测定支气管肺泡灌洗液（BALF）中细胞因子表达。在体外细胞培养模型中，本研究采用特异性抑制剂分析参与KSRP介导的哮喘发病机制作用的细胞信号通路。
结果：与野生型小鼠相比，KSRP缺乏会加剧OVA诱导的过敏性哮喘，表现为AHR增加、肺损伤加重、杯状细胞增生和OVA特异性抗体产生增加。CBA分析证实，KSRP缺乏会上调BALF中IL-4、IL-5和IL-13生成。KSRP对Th2相关细胞因子表达的影响似可能通过调节STAT6和NFAT信号通路介导，而非通过抑制编码细胞因子的mRNA物种的稳定性。
结论：本研究数据表明，KSRP可抑制Th2免疫细胞活性，因此可能对Th2介导疾病的发病机制至关重要。
The RNA-binding protein KSRP reduces asthma-like characteristics in a murine model.
Palzer KA, Bolduan V, Lakus J, Tubbe I, Montermann E, Clausen BE, Bros M, Pautz A.
Abstract
BACKGROUND:Asthma is a chronic inflammatory disease characterized by dysregulated cytokine expression. The RNA-binding protein KSRP reduces the expression of several pro-inflammatory mediators.
OBJECTIVE:Therefore, we investigated whether KSRP modulates Th2-associated immune responses in vivo in an ovalbumin-induced (OVA) allergic asthma model in C57BL/6 KSRP-deficient mice (KSRP-/-).
METHODS:Asthma severity in OVA-immunized wild type or KSRP-/- mice was determined by airway hyperresponsiveness (AHR), structural changes of lung tissue, and OVA-specific antibody production. Cytokine expression in bronchoalveolar lavage fluid (BALF) was measured by Cytometric Bead Array (CBA) analysis. Cellular signaling pathways involved in KSRP-mediated effects in asthma pathogenesis were analyzed in vitro in cell culture models using specific inhibitors.
RESULTS:KSRP deficiency exacerbates OVA-induced allergic asthma compared to wild type mice, as indicated by increased AHR, more severe lung damage, goblet cell hyperplasia and increased OVA-specific antibody production. CBA analyses confirmed, that KSRP deficiency enhances IL-4, IL-5 and IL-13 production in BALF. The effect of KSRP on Th2-associated cytokine expression appears to be mediated by modulation of the STAT6 and NFAT signaling pathway rather than by inhibiting the stability of cytokine-encoding mRNA species.
CONCLUSION:Our data demonstrate that KSRP dampens Th2 immune cell activity and therefore seems to be important for the pathogenesis of Th2-mediated diseases.
背景：哮喘是一种慢性炎症性疾病，其特征是细胞因子表达失调。RNA结合蛋白KSRP可降低几种促炎介质表达。
目的：因此，本研究旨在研究KSRP可调节卵清蛋白（OVA）诱导过敏性哮喘模型C57BL/6 KSRP缺陷小鼠（KSRP-/-）体内Th2相关免疫反应。
方法：本研究通过测定气道高反应性（AHR）、肺组织结构变化和OVA特异性抗体水平以评估OVA致敏野生型或KSRP-/-小鼠的哮喘严重程度。通过细胞计数珠阵列（CBA）分析测定支气管肺泡灌洗液（BALF）中细胞因子表达。在体外细胞培养模型中，本研究采用特异性抑制剂分析参与KSRP介导的哮喘发病机制作用的细胞信号通路。
结果：与野生型小鼠相比，KSRP缺乏会加剧OVA诱导的过敏性哮喘，表现为AHR增加、肺损伤加重、杯状细胞增生和OVA特异性抗体产生增加。CBA分析证实，KSRP缺乏会上调BALF中IL-4、IL-5和IL-13生成。KSRP对Th2相关细胞因子表达的影响似可能通过调节STAT6和NFAT信号通路介导，而非通过抑制编码细胞因子的mRNA物种的稳定性。
结论：本研究数据表明，KSRP可抑制Th2免疫细胞活性，因此可能对Th2介导疾病的发病机制至关重要。
（中日友好医院呼吸与危重症医学科 张婧媛 摘译 林江涛 审校）
（Inflamm Res. 2025 Mar 17;74(1):54. doi: 10.1007/s00011-025-02024-5.）
（Inflamm Res. 2025 Mar 17;74(1):54. doi: 10.1007/s00011-025-02024-5.）
The RNA-binding protein KSRP reduces asthma-like characteristics in a murine model.
Palzer KA, Bolduan V, Lakus J, Tubbe I, Montermann E, Clausen BE, Bros M, Pautz A.
Abstract
BACKGROUND:Asthma is a chronic inflammatory disease characterized by dysregulated cytokine expression. The RNA-binding protein KSRP reduces the expression of several pro-inflammatory mediators.
OBJECTIVE:Therefore, we investigated whether KSRP modulates Th2-associated immune responses in vivo in an ovalbumin-induced (OVA) allergic asthma model in C57BL/6 KSRP-deficient mice (KSRP-/-).
METHODS:Asthma severity in OVA-immunized wild type or KSRP-/- mice was determined by airway hyperresponsiveness (AHR), structural changes of lung tissue, and OVA-specific antibody production. Cytokine expression in bronchoalveolar lavage fluid (BALF) was measured by Cytometric Bead Array (CBA) analysis. Cellular signaling pathways involved in KSRP-mediated effects in asthma pathogenesis were analyzed in vitro in cell culture models using specific inhibitors.
RESULTS:KSRP deficiency exacerbates OVA-induced allergic asthma compared to wild type mice, as indicated by increased AHR, more severe lung damage, goblet cell hyperplasia and increased OVA-specific antibody production. CBA analyses confirmed, that KSRP deficiency enhances IL-4, IL-5 and IL-13 production in BALF. The effect of KSRP on Th2-associated cytokine expression appears to be mediated by modulation of the STAT6 and NFAT signaling pathway rather than by inhibiting the stability of cytokine-encoding mRNA species.
CONCLUSION:Our data demonstrate that KSRP dampens Th2 immune cell activity and therefore seems to be important for the pathogenesis of Th2-mediated diseases.
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