Department of Chemical Pharmacology and Toxicology, Faculty of Chemical and Pharmaceutical Sciences, University of Chile, Santos Dumont 964, Independencia, Santiago, Chile.
Department of Pharmacology, Toxicology and Pharmacodependence, Pharmacy Faculty, University of Costa Rica, San José, Costa Rica.
Mol Biol Rep. 2021 Jan;48(1):57-66. doi: 10.1007/s11033-020-06133-8. Epub 2021 Jan 18.
Cardiac fibroblasts (CFs) have a key role in the inflammatory response after cardiac injury and are necessary for wound healing. Resolvins are potent agonists that control the duration and magnitude of inflammation. They decrease mediators of pro-inflammatory expression, reduce neutrophil migration to inflammation sites, promote the removal of microbes and apoptotic cells, and reduce exudate. However, whether resolvins can prevent pro-inflammatory-dependent effects in CFs is unknown. Thus, the present work was addressed to study whether resolvin D1 and E1 (RvD1 and RvE1) can prevent pro-inflammatory effects on CFs after lipopolysaccharide (LPS) challenge. For this, CFs were stimulated with LPS, in the presence or absence of RvD1 or RvE1, to analyze its effects on intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion protein 1 (VCAM-1), monocyte adhesion and the cytokine levels of tumor necrosis factor alpha (TNF-α), interleukin-6(IL-6), interleukin-1beta (IL-1β), monocyte chemoattractant protein-1 (MCP-1) and interleukin-10 (IL-10). Our results showed that CFs are expressing ALX/FPR2 and ChemR23, RvD1 and RvE1 receptors, respectively. RvD1 and RvE1 prevent the increase of ICAM-1 and VCAM-1 protein levels and the adhesion of spleen mononuclear cells to CFs induced by LPS. Finally, RvD1, but not RvE1, prevents the LPS-induced increase of IL-6, MCP-1, TNF-α, and IL-10. In conclusion, our findings provide evidence that in CFs, RvD1 and RvE1 might actively participate in the prevention of inflammatory response triggered by LPS.
心肌成纤维细胞（CFs）在心损伤后的炎症反应中起着关键作用，并且是伤口愈合所必需的。解析素是控制炎症持续时间和程度的有效激动剂。它们降低促炎表达的介质，减少中性粒细胞向炎症部位迁移，促进微生物和凋亡细胞的清除，并减少渗出物。然而，解析素是否可以防止 CFs 中促炎依赖的作用尚不清楚。因此，本研究旨在研究解析素 D1 和 E1（RvD1 和 RvE1）是否可以防止脂多糖（LPS）刺激后 CFs 的促炎作用。为此，用 LPS 刺激 CFs，在存在或不存在 RvD1 或 RvE1 的情况下，分析其对细胞间黏附分子 1（ICAM-1）、血管细胞黏附蛋白 1（VCAM-1）、单核细胞黏附和肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）、白细胞介素-1β（IL-1β）、单核细胞趋化蛋白-1（MCP-1）和白细胞介素-10（IL-10）的影响。我们的结果表明，CFs 表达 ALX/FPR2 和 ChemR23，分别为 RvD1 和 RvE1 受体。RvD1 和 RvE1 可防止 LPS 诱导的 ICAM-1 和 VCAM-1 蛋白水平增加以及脾单核细胞与 CFs 的黏附。最后，RvD1（而非 RvE1）可防止 LPS 诱导的 IL-6、MCP-1、TNF-α和 IL-10 增加。总之，我们的研究结果提供了证据，表明在 CFs 中，RvD1 和 RvE1 可能积极参与由 LPS 触发的炎症反应的预防。
