Department of Endodontics, University of Nantes, Nantes, France.
Centre de Recherche en Transplantation et Immunologie UMR1064, INSERM, Université de Nantes, Nantes, France.
Sci Rep. 2018 Jun 11;8(1):8921. doi: 10.1038/s41598-018-27194-7.
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 (LXA) has been implicated as an anti-inflammatory, pro-resolving mediator. We hypothesized that LXA 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, LXA 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 LXA. Finally, LXA enhanced immunomodulatory properties of SCAP towards Peripheral Blood Mononuclear Cells. These findings provide the first evidence that the LXA-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.
类似于炎症的起始阶段，其消退是一个通过一系列介质协调和调节的过程。脂氧素 A4（LXA）已被认为是一种抗炎、促解决的介质。我们假设 LXA 通过根尖乳头干细胞（SCAP）的免疫抑制活性来减弱或预防炎症反应。在这里，我们首次在体外报告，在 SCAP 群体中，脂氧素受体 ALX/FPR2 被持续表达，并在受到脂多糖和/或 TNF-α刺激后上调。此外，LXA 通过激活其受体 ALX/FPR2，显著增强了 SCAP 的增殖、迁移和伤口愈合能力。LXA 以剂量依赖的方式抑制 SCAP 细胞因子、趋化因子和生长因子的分泌。最后，LXA 增强了 SCAP 对外周血单个核细胞的免疫调节特性。这些发现为 SCAP 中的 LXA-ALX/FPR2 轴调节炎症介质和增强免疫调节特性提供了第一个证据。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，并为 ALX/FPR2 受体增强干细胞介导的促解决途径提供了一个新的分子靶点。
