Lipoxin A(4) Attenuates the Inflammatory Response in Stem Cells of the Apical Papilla via ALX/FPR2.
Lipoxin A(4) Attenuates the Inflammatory Response in Stem Cells of the Apical Papilla via ALX/FPR2.
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DOI：
10.1038/s41598-018-27194-7
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发表时间：
2018-06-11
影响因子：
4.6
通讯作者：
Peters OA
中科院分区：
文献类型：
--
作者：
Gaudin A;Tolar M;Peters OA
与炎症的发作阶段相似，其消退是一个以一组介质协调和调节的方式展开的过程。脂氧素A4（LXA 4）被认为是一种抗炎、促消退的介质。我们假设LXA 4通过顶乳头干细胞（SCAP）的免疫抑制活性减弱或预防炎症反应。在此，我们首次在体外报告了在SCAP人群中，脂氧素受体ALX/FPR 2在脂多糖和/或TNF-α刺激后组成性表达并上调。此外，LXA 4通过激活其受体ALX/FPR 2显著增强SCAP的增殖、迁移和伤口愈合能力。细胞因子，趋化因子和生长因子分泌的SCAP被LXA 4以剂量依赖性的方式抑制。最后，LXA 4增强SCAP对外周血单核细胞的免疫调节特性。这些发现提供了SCAP中LXA 4-ALX/FPR 2轴调节炎症介质并增强免疫调节特性的第一个证据。SCAP的这些特征也可能支持这些细胞在炎症消退阶段的作用，并提示ALX/FPR 2受体的新分子靶点，以增强干细胞介导的促消退途径。
Similar to the onset phase of inflammation, its resolution is a process that unfolds in a manner that is coordinated and regulated by a panel of mediators. Lipoxin A4 (LXA4) has been implicated as an anti-inflammatory, pro-resolving mediator. We hypothesized that LXA4 attenuates or prevents an inflammatory response via the immunosuppressive activity of Stem Cells of the Apical Papilla (SCAP). Here, we report for the first time in vitro that in a SCAP population, lipoxin receptor ALX/FPR2 was constitutively expressed and upregulated after stimulation with lipopolysaccharide and/or TNF-α. Moreover, LXA4 significantly enhanced proliferation, migration, and wound healing capacity of SCAP through the activation of its receptor, ALX/FPR2. Cytokine, chemokine and growth factor secretion by SCAP was inhibited in a dose dependent manner by LXA4. Finally, LXA4 enhanced immunomodulatory properties of SCAP towards Peripheral Blood Mononuclear Cells. These findings provide the first evidence that the LXA4-ALX/FPR2 axis in SCAP regulates inflammatory mediators and enhances immunomodulatory properties. Such features of SCAP may also support the role of these cells in the resolution phase of inflammation and suggest a novel molecular target for ALX/FPR2 receptor to enhance a stem cell-mediated pro-resolving pathway.
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影响因子：
4.2
作者：
Liu, Jing-Yi;Chen, Xue;Zou, Xiao-Ying
通讯作者：
Zou, Xiao-Ying
影响因子：
5.6
作者：
Ding, Gang;Wang, Wei;Wang, Songlin
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影响因子：
5.1
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影响因子：
2.4
作者：
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通讯作者：
Hematti P
影响因子：
6.2
作者：
Fang, Lubin;Lange, Claudia;Fehse, Boris
通讯作者：
Fehse, Boris