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Differential signaling patterns of stimulated bone marrow-derived dendritic cells under α1-antitrypsin-enriched conditions
Cellular Immunology ( IF 4.3 ) Pub Date : 2021-01-01 , DOI: 10.1016/j.cellimm.2020.104281
Eyal Ozeri 1 , Peleg Rider 1 , Shoham Rigbi 1 , Galit Shahaf 1 , Iulia I Nita 2 , Israel Sekler 2 , Eli C Lewis 1 , Ronen Schuster 1
Affiliation  

Dendritic cells (DCs) mature upon an inflammatory trigger. However, an inflammatory trigger can lead to a semi-mature phenotype, allowing DCs to evoke tolerance and expedite the resolution of inflammation. This duality likely involves context-dependent modulation of inflammatory signaling. Human α1-antitrypsin (hAAT) promotes semimature DCs. We examined changes in a wide spectrum of signaling cascades in stimulated murine bone marrow-derived cells with hAAT. Upon stimulation by IL-1β+IFNγ, hAAT-treated cells depicted an attenuated calcium flux. Disrupting PKA or NF-κB pathways revoked only some hAAT-mediated outcomes. hAAT-treated cells exhibited a distict pattern of kinase phosphorylation. hAAT-mediated increase in Treg cells in-vitro required intact inflammatory signaling pathways. Taken together, hAAT appears to require a stimulated microenvironment to promote inflammatory resolution, setting it aside from classical anti-inflammatory agents. Further studies are required to identify the specific molecules targeted by hAAT that mediate these and other outcomes.



中文翻译:

富含α1-抗胰蛋白酶的条件下刺激的骨髓来源树突状细胞的差异信号模式

树突状细胞(DC)在炎症触发时成熟。然而,炎性触发可导致半成熟表型,使DC引起耐受性并加快炎症消退。这种双重性可能涉及炎性信号传导的背景依赖性调节。人α1-抗胰蛋白酶(hAAT)促进半成熟DC。我们检查了hAAT刺激的小鼠骨髓来源的细胞中广泛的信号级联的变化。在受到IL-1β+IFNγ刺激后,经hAAT处理的细胞显示出钙通量降低。破坏PKA或NF-κB通路仅撤销了一些hAAT介导的结果。经hAAT处理的细胞表现出激酶磷酸化的离散模式。hAAT介导的体外Treg细胞增加需要完整的炎症信号通路。在一起 hAAT似乎需要刺激的微环境来促进炎症消退,除了经典的消炎药外。需要进一步的研究来鉴定hAAT靶向的介导这些和其他结果的特定分子。

更新日期:2021-01-14
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