木犀草素通过抑制IL-36γ分泌介导的MAPK通路缓解中性粒细胞性哮喘
2023/04/21
摘要
背景：木犀草素可影响多种生物功能，如抗炎、抗氧化和免疫增强过程。木犀草素可抑制T2-高哮喘的炎症反应，但其在中性粒细胞性哮喘中的作用研究尚不充分。
目的：本研究确定木犀草素对中性粒细胞性哮喘中IL-36γ分泌介导的MAPK通路信号的影响。
方法：采用卵清蛋白/脂多糖(OVA/LPS)建立哮喘模型。雌性6-8周龄C57BL/6小鼠分为对照组、哮喘组、木犀草素(20 mg/kg)组和哮喘+木犀草素(20 mg/kg)组。为探讨木犀草素对中性粒细胞性哮喘的抗炎作用机制，分别采用木犀草素(20 mmol/L)、LPS (100 ng/mL)、重组人IL-36γ蛋白(rhIL-36γ;100 ng/mL)或IL-36γsiRNA对Beas-2B细胞进行刺激。
结果：与对照组相比，哮喘模型小鼠IL-36γ分泌和MAPK/IL-1β信号通路显著增加(p＜0.05)。然而，木犀草素降低了IL-36γ分泌水平和MAPK/IL-1β信号通路(p＜0.05)。此外，木犀草素抑制LPS (100 ng/mL)刺激Beas-2B细胞后IL-36γ和MAPK/IL-1β的水平(p＜0.05)。我们发现，在Beas-2B细胞中，木犀草素在rhIL-36γ刺激后抑制了MAPK通路的激活和IL-1β的分泌(100 ng/mL;p＜0.05)。最后，IL-1β和磷酸化的MAPK水平在IL-36γ siRNA + LPS组(100 ng/mL)中低于非特异性对照(NC) siRNA + LPS组(p＜0.05)。
结论：木犀草素通过抑制IL-36γ分泌介导的MAPK通路缓解中性粒细胞性哮喘。这些发现为木犀草素在中性粒细胞性哮喘治疗中的应用提供了理论依据方法。
Luteolin alleviated neutrophilic asthma by inhibiting IL-36γ secretion-mediated MAPK pathways
Xin-rui Qiao, Tao Feng, Dong Zhang, Li-li Zhi, Jin-tao Zhang, Xiao-fei Liu, Yun Pan, Jia-wei Xu, Wen-Jing Cui & Liang Dong
Abtract
BACKGROUND:Luteolin can affect multiple biological functions, such as anti-inflammatory, antioxidant and immune enhancement processes. Luteolin can inhibit inflammation of T2-high asthma, but its role in neutrophilic asthma has been insufficently studied.
OBJECTIVE: This study determines the effect of luteolin on IL-36γ secretion-mediated MAPK pathway signalling in neutrophilic asthma.
METHODS:The asthma model was established by using ovalbumin/lipopolysaccharide (OVA/LPS). Female 6–8-week-old C57BL/6 mice were divided into control, asthma, luteolin (20 mg/kg) and asthma+luteolin (20 mg/kg) groups. To explore the mechanism of anti-inflammatory effects of luteolin in neutrophilic asthma, Beas-2B cells were treated with luteolin (20 mmol/L), LPS (100 ng/mL), recombinant human IL-36γ protein (rhIL-36γ; 100 ng/mL) or IL-36γ siRNA.
RESULTS: IL-36γ secretion and MAPK/IL-1β signalling were significantly increased in the asthma mouse model compared with the control (p<0.05). However, the levels of IL-36γ secretion and MAPK/IL-1β signalling were reduced by luteolin (p< 0.05). In addition, luteolin inhibited IL-36γ and MAPK/IL-1β levels after LPS (100 ng/mL) stimulation of Beas-2B cells (p< 0.05). We found that in Beas-2B cells, luteolin inhibited activation of the MAPK pathway and IL-1βsecretion following stimulation with rhIL-36γ (100 ng/mL; p< 0.05). Finally, IL-1β and phosphorylated MAPK levels were found to be lower in the IL-36γ siRNA＋LPS (100 ng/mL) group than in the nonspecific control (NC) siRNA＋LPS group (p< 0.05).
CONCLUSIONS: Luteolin alleviated neutrophilic asthma by inhibiting IL-36γ secretion-mediated MAPK pathways. These findings provided a theoretical basis for the application of luteolin in the treatment of neutrophilic asthma
背景：木犀草素可影响多种生物功能，如抗炎、抗氧化和免疫增强过程。木犀草素可抑制T2-高哮喘的炎症反应，但其在中性粒细胞性哮喘中的作用研究尚不充分。
目的：本研究确定木犀草素对中性粒细胞性哮喘中IL-36γ分泌介导的MAPK通路信号的影响。
方法：采用卵清蛋白/脂多糖(OVA/LPS)建立哮喘模型。雌性6-8周龄C57BL/6小鼠分为对照组、哮喘组、木犀草素(20 mg/kg)组和哮喘+木犀草素(20 mg/kg)组。为探讨木犀草素对中性粒细胞性哮喘的抗炎作用机制，分别采用木犀草素(20 mmol/L)、LPS (100 ng/mL)、重组人IL-36γ蛋白(rhIL-36γ;100 ng/mL)或IL-36γsiRNA对Beas-2B细胞进行刺激。
结果：与对照组相比，哮喘模型小鼠IL-36γ分泌和MAPK/IL-1β信号通路显著增加(p＜0.05)。然而，木犀草素降低了IL-36γ分泌水平和MAPK/IL-1β信号通路(p＜0.05)。此外，木犀草素抑制LPS (100 ng/mL)刺激Beas-2B细胞后IL-36γ和MAPK/IL-1β的水平(p＜0.05)。我们发现，在Beas-2B细胞中，木犀草素在rhIL-36γ刺激后抑制了MAPK通路的激活和IL-1β的分泌(100 ng/mL;p＜0.05)。最后，IL-1β和磷酸化的MAPK水平在IL-36γ siRNA + LPS组(100 ng/mL)中低于非特异性对照(NC) siRNA + LPS组(p＜0.05)。
结论：木犀草素通过抑制IL-36γ分泌介导的MAPK通路缓解中性粒细胞性哮喘。这些发现为木犀草素在中性粒细胞性哮喘治疗中的应用提供了理论依据方法。
（中日友好医院呼吸与危重症医学科 李春晓 摘译 林江涛 审校）
（Pharmaceutical Biology, 61:1, 165-176, DOI: 10.1080/13880209.2022.2160770）
（Pharmaceutical Biology, 61:1, 165-176, DOI: 10.1080/13880209.2022.2160770）
Luteolin alleviated neutrophilic asthma by inhibiting IL-36γ secretion-mediated MAPK pathways
Xin-rui Qiao, Tao Feng, Dong Zhang, Li-li Zhi, Jin-tao Zhang, Xiao-fei Liu, Yun Pan, Jia-wei Xu, Wen-Jing Cui & Liang Dong
Abtract
BACKGROUND:Luteolin can affect multiple biological functions, such as anti-inflammatory, antioxidant and immune enhancement processes. Luteolin can inhibit inflammation of T2-high asthma, but its role in neutrophilic asthma has been insufficently studied.
OBJECTIVE: This study determines the effect of luteolin on IL-36γ secretion-mediated MAPK pathway signalling in neutrophilic asthma.
METHODS:The asthma model was established by using ovalbumin/lipopolysaccharide (OVA/LPS). Female 6–8-week-old C57BL/6 mice were divided into control, asthma, luteolin (20 mg/kg) and asthma+luteolin (20 mg/kg) groups. To explore the mechanism of anti-inflammatory effects of luteolin in neutrophilic asthma, Beas-2B cells were treated with luteolin (20 mmol/L), LPS (100 ng/mL), recombinant human IL-36γ protein (rhIL-36γ; 100 ng/mL) or IL-36γ siRNA.
RESULTS: IL-36γ secretion and MAPK/IL-1β signalling were significantly increased in the asthma mouse model compared with the control (p<0.05). However, the levels of IL-36γ secretion and MAPK/IL-1β signalling were reduced by luteolin (p< 0.05). In addition, luteolin inhibited IL-36γ and MAPK/IL-1β levels after LPS (100 ng/mL) stimulation of Beas-2B cells (p< 0.05). We found that in Beas-2B cells, luteolin inhibited activation of the MAPK pathway and IL-1βsecretion following stimulation with rhIL-36γ (100 ng/mL; p< 0.05). Finally, IL-1β and phosphorylated MAPK levels were found to be lower in the IL-36γ siRNA＋LPS (100 ng/mL) group than in the nonspecific control (NC) siRNA＋LPS group (p< 0.05).
CONCLUSIONS: Luteolin alleviated neutrophilic asthma by inhibiting IL-36γ secretion-mediated MAPK pathways. These findings provided a theoretical basis for the application of luteolin in the treatment of neutrophilic asthma
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