KIF2A decreases IL-33 production and attenuates allergic asthmatic inflammation.
KIF2A decreases IL-33 production and attenuates allergic asthmatic inflammation.
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KIF 2A减少IL-33的产生并减弱过敏性哮喘炎症。
DOI：
10.1186/s13223-022-00697-9
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发表时间：
2022-06-19
期刊：
影响因子：
--
通讯作者：
中科院分区：
文献类型：
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作者：
微管依赖性分子马达蛋白Kinesin家族成员2A（KIF 2A）在哮喘人气道上皮中下调。然而，KIF 2A在哮喘中的作用以及可能的潜在机制知之甚少。给予屋尘螨（HDM）提取物以建立哮喘小鼠模型。检测KIF 2A、IL-33的表达及自噬途径。用质粒pCMV-KIF 2A在体外和体内气道上皮细胞中过表达KIF 2A。测定支气管肺泡灌洗液（BALF）和肺组织匀浆中IL-4、IL-5、IL-33等细胞因子的含量。在体外和体内，气道上皮细胞在应对屋尘螨（HDM）的挑战时，显示KIF 2A的产生减少。同时，自噬和IL-33在HMD处理的上皮细胞中增加。从机制上讲，KIF 2A通过抑制HDM处理的上皮细胞中的mTORC 1通路来减少自噬，这有助于减少IL-33的产生。此外，体内KIF 2A转染减少了肺中的IL-33和自噬，导致变应性哮喘的减弱。KIF 2A抑制mTORC 1介导的自噬，并减少过敏性气道炎症中上皮源性细胞因子IL-33的产生。这些数据表明KIF 2A可能是过敏性哮喘的新靶点。在线版本包含补充材料，可通过10.1186/s13223-022-00697-9获得。
The microtubule-dependent molecular motor protein Kinesin Family Member 2A (KIF2A) is down-regulated in asthmatic human airway epithelium. However, little is known about the roles of KIF2A as well as the possible underlying mechanisms in asthma. House dust mite (HDM) extract was administered to establish a murine model of asthma. The expression of KIF2A, IL-33 and the autophagy pathways were detected. The plasmid pCMV-KIF2A was used to overexpress KIF2A in the airway epithelial cells in vitro and in vivo. IL-4, IL-5, IL-33 and other cytokines in bronchoalveolar lavage fluid (BALF) and lung tissues homogenates were measured. In response to the challenge of house dust mite (HDM) in vitro and in vivo, airway epithelial cells displayed decreased production of KIF2A. Meanwhile, autophagy and IL-33 were increased in HMD-treated epithelial cells. Mechanistically, KIF2A decreased autophagy via suppressing mTORC1 pathway in HDM-treated epithelial cells, which contributed to the reduced production of IL-33. Moreover, in vivo KIF2A transfection reduced IL-33 and autophagy in the lung, leading to the attenuation of allergic asthma. KIF2A suppressed mTORC1-mediated autophagy and decreased the production of epithelial-derived cytokine IL-33 in allergic airway inflammation. These data indicate that KIF2A may be a novel target in allergic asthma. The online version contains supplementary material available at 10.1186/s13223-022-00697-9.
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DOI：
10.1073/pnas.0812690106
发表时间：
2009-06-02
影响因子：
11.1
作者：
Cayrol, Corinne;Girard, Jean-Philippe
通讯作者：
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影响因子：
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DOI：
10.1083/jcb.108.3.855
发表时间：
1989-03
期刊：
The Journal of cell biology
影响因子：
--
作者：
Heuser J
通讯作者：
Heuser J
影响因子：
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作者：
Bai J;Smock SL;Jackson GR Jr;MacIsaac KD;Huang Y;Mankus C;Oldach J;Roberts B;Ma YL;Klappenbach JA;Crackower MA;Alves SE;Hayden PJ
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影响因子：
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