CNRS UMR 9017, Inserm U1019, CIIL-Center for Infection and Immunity of Lille (C.D., P.M., V.L., C.G.), CHU Lille, Institut Pasteur de Lille, University Lille, France.
Inserm U1011-EGID (B.G.), CHU Lille, Institut Pasteur de Lille, University Lille, France.
Arterioscler Thromb Vasc Biol. 2020 Nov;40(11):2619-2631. doi: 10.1161/ATVBAHA.120.314832. Epub 2020 Sep 10.
The occurrence of new blood vessel formation in the lungs of asthmatic patients suggests a critical role for airway endothelial cells (ECs) in the disease. IL-33 (Interleukin-33)-a cytokine abundantly expressed in human lung ECs-recently emerged as a key factor in the development of allergic diseases, including asthma. In the present study, we evaluated whether mouse and human ECs exposed to the common allergen produce IL-33 and characterized the activated signaling pathways. Approach and Results: Mouse primary lung ECs were exposed in vitro to extract or rmIL-33 (recombinant murine IL-33). Both and rmIL-33 induced transcription without increasing the IL-33 production and upregulated the expression of its receptor, as well as genes involved in angiogenesis and the regulation of immune responses. In particular, and rmIL-33 upregulated transcript level, yet without promoting apoptosis. Inhibition of caspases involved in the Fas signaling pathway, increased IL-33 protein level in ECs, suggesting that Fas may decrease IL-33 level through caspase-8-dependent mechanisms. Our data also showed that the NF-κB (nuclear factor-κB), PI3K/Akt, and Wnt/β-catenin pathways regulate transcription in both mouse and human primary ECs.
Herein, we described a new mechanism involved in the control of IL-33 production in lung ECs exposed to allergens.
哮喘患者肺部新血管的形成表明气道内皮细胞（ECs）在疾病中起着关键作用。IL-33（白细胞介素-33）-一种在人肺 ECs 中大量表达的细胞因子-最近成为包括哮喘在内的过敏疾病发展的关键因素。在本研究中，我们评估了暴露于常见过敏原的小鼠和人 EC 是否产生 IL-33，并对激活的信号通路进行了表征。
体外将小鼠原代肺 EC 暴露于 提取物或 rmIL-33（重组鼠 IL-33）中。和 rmIL-33 均诱导转录，而不增加 IL-33 的产生，并上调其受体以及参与血管生成和免疫反应调节的基因的表达。特别是，和 rmIL-33 上调了转录水平，但没有促进细胞凋亡。Fas 信号通路中参与 Fas 信号通路的半胱天冬酶的抑制作用增加了 ECs 中的 IL-33 蛋白水平，这表明 Fas 可能通过 caspase-8 依赖性机制降低 IL-33 水平。我们的数据还表明，NF-κB（核因子-κB）、PI3K/Akt 和 Wnt/β-catenin 通路调节小鼠和人原代 ECs 中的转录。
本文描述了一种新的机制，该机制涉及到暴露于过敏原的肺 ECs 中 IL-33 产生的控制。
