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Resolvin D1 and E1 promote resolution of inflammation in rat cardiac fibroblast in vitro

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Abstract

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.

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Funding

This work was supported by FONDECYT grant 1170425 from “Agencia Nacional de Investigación y Desarrollo de Chile (ANID)”, and fellowships OAICE-CAB-03-031-2015 from “Universidad de Costa Rica” and PED-118-2015-I from “Ministerio de Ciencia, Tecnología y Telecomunicaciones de Costa Rica”.

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Authors and Affiliations

  1. Department of Chemical Pharmacology and Toxicology, Faculty of Chemical and Pharmaceutical Sciences, University of Chile, Santos Dumont 964, Independencia, Santiago, Chile

    Aimeé Salas-Hernández, Claudio Espinoza-Pérez, Jenaro Espitia-Corredor, José Lillo, Pablo Parra-Flores & Guillermo Díaz-Araya

  2. Department of Pharmacology, Toxicology and Pharmacodependence, Pharmacy Faculty, University of Costa Rica, San José, Costa Rica

    Aimeé Salas-Hernández

  3. Advanced Center for Chronic Diseases (ACCDiS), Faculty of Chemical and Pharmaceutical Sciences and Faculty of Medicine, University of Chile, Santos Dumont 964, Independencia, Santiago, Chile

    Guillermo Díaz-Araya

  4. Pharmacology Program, Biomedical Sciences Institute, University of Chile, Independencia 1027, Independencia, Santiago, Chile

    Raúl Vivar

  5. Department of Pharmacology, Faculty of Medicine, Universidad Autónoma de Madrid and Instituto de Investigación Sanitaria Hospital Universitario La Paz (IdiPAZ), Madrid, Spain

    Carlos F. Sánchez-Ferrer & Concepción Peiró

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  1. Aimeé Salas-Hernández
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Contributions

Aimée Salas-Hernández: Conceptualization, Methodology, Formal analysis, Investigation, Resources, Writing—Original Draft, Writing—Review & Editing. Claudio Espinoza: Methodology, Investigation, Formal analysis. Raúl Vivar: Methodology. Jenaro Espitia-Corredor: Methodology. José Lillo: Methodology. Pablo Parra-Flores: Methodology. Carlos Sánchez Ferrer: Conceptualization, Methodology, Writing—Review & Editing Resources. Cocepción Peiró: Conceptualization, Methodology, Investigation, Writing—Review & Editing. Diaz-Araya G: Conceptualization, Methodology, Investigation, Writing—Review & Editing, Supervision Project administration, funding acquisition.

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Correspondence to Guillermo Díaz-Araya.

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Experimental protocols following international Guiding Principles for Biomedical Research Involving Animals were approved by the Bioethics Committee for Animal Research of the Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile (CBE2017-08).

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Salas-Hernández, A., Espinoza-Pérez, C., Vivar, R. et al. Resolvin D1 and E1 promote resolution of inflammation in rat cardiac fibroblast in vitro. Mol Biol Rep 48, 57–66 (2021). https://doi.org/10.1007/s11033-020-06133-8

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