Interleukin-1α Is a Critical Mediator of the Response of Human Bronchial Fibroblasts to Eosinophilic Inflammation.
Interleukin-1α Is a Critical Mediator of the Response of Human Bronchial Fibroblasts to Eosinophilic Inflammation.
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DOI：
10.3390/cells10030528
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发表时间：
2021-03-02
期刊：
影响因子：
6
通讯作者：
Sandbo N
中科院分区：
文献类型：
--
作者：
Bernau K;Leet JP;Floerke H;Bruhn EM;Noll AL;McDermott IS;Esnault S;Jarjour NN;Sandbo N
嗜酸性粒细胞在哮喘中的过敏性炎症部分是通过复杂的可溶性介质环境的细化。人支气管成纤维细胞（HBF）对这些介质的刺激作出反应，通过获得促炎谱，包括诱导白细胞介素6 （IL6）和IL8。本研究旨在确定介导HBF中il - 6和il - 8诱导的嗜酸性可溶性因子的关键成分。用嗜酸性粒细胞衍生的可溶性介质处理HBF，分析其基因表达、细胞内信号传导以及炎症信号抑制后IL6和IL8的分泌情况。对轻度哮喘患者进行节段性变应原支气管激发（SBP-Ag）检测，并对支气管肺泡灌洗液进行嗜酸性粒细胞和细胞因子检测。我们发现，通过il- 1α/ il- 1受体的信号传导是HBF对嗜酸性粒细胞衍生的可溶性因子反应的重要组成部分。激活B细胞的核因子κ轻链增强子（NFκB）信号通路依赖于il - 1α的激活，从而诱导il - 6的分泌。然而，在诱导IL8的过程中，NFκB信号是不需要的，而Src则是必需的。il - 1α与SBP-Ag后人气道嗜酸性粒细胞炎症有关。结论：il- 1α似乎是可溶性嗜酸性粒细胞来源环境的关键组成部分，该环境驱动促炎性支气管成纤维细胞反应，并与SBP-Ag后的嗜酸性粒细胞炎症相关。il - 1α-信号的破坏可改变嗜酸性粒细胞炎症对气道重塑的下游作用。
Eosinophils contribute to allergic inflammation in asthma in part via elaboration of a complex milieu of soluble mediators. Human bronchial fibroblasts (HBF) respond to stimulation by these mediators by acquiring a pro-inflammatory profile including induction of interleukin 6 (IL6) and IL8. This study sought to determine key component(s) of eosinophil soluble factors that mediate IL6 and IL8 induction in HBF. HBF treated with eosinophil-derived soluble mediators were analyzed for gene expression, intracellular signaling, and IL6 and IL8 secretion following inhibition of inflammatory signaling. Segmental allergen bronchoprovocation (SBP-Ag) was performed in mild asthmatics and bronchoalveolar lavage fluid was analyzed for eosinophils and cytokines. We found that signaling via the IL1α/IL1 receptor is an essential component of the response of HBF to eosinophil-derived soluble factors. IL1α-dependent activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB) signaling is required to induce IL6 secretion. However, NFκB signaling is dispensable for the induction of IL8, whereas Src is required. IL1α is associated with eosinophilic inflammation in human airways after SBP-Ag. Conclusions: IL1α appears to be a critical component of the soluble eosinophil-derived milieu that drives pro-inflammatory bronchial fibroblast responses and associates with eosinophilic inflammation following SBP-Ag. Disruption of IL1α-signaling could modify the downstream effects of eosinophilic inflammation on airway remodeling.
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