title: The anti-inflammatory and pro-resolution effects of aspirin-triggered RvD1 (AT-RvD1) on peripheral blood mononuclear cells from patients with severe asthma.
abstract: Asthma is an inflammatory disease that is characterized by a predominance of eosinophils and/or neutrophils in the airways. In the resolution of inflammation, lipid mediators such as resolvin D1 (RvD1) and its epimer aspirin-triggered RvD1 (AT-RvD1) are produced and demonstrate anti-inflammatory and pro-resolution effects. In experimental models such as airway allergic inflammation induced by ovalbumin in mice, RvD1 and AT-RvD1 alleviate some of the most important phenotypes of asthma. Here, we demonstrated the effects of AT-RvD1 on peripheral blood mononuclear cells (PBMCs) from healthy individuals and patients with severe asthma stimulated with lipopolysaccharide (LPS) or Dermatophagoides pteronyssinus (DM). AT-RvD1 (100nM) reduced the concentration of TNF-α in PBMCs from healthy individuals and patients with severe asthma stimulated with LPS or DM. In addition, AT-RvD1 lowered the production of IL-10 only in PBMCs from patients with severe asthma stimulated with LPS. These effects were associated in part with decreasing NF-κB activation. Moreover, AT-RvD1 significantly increased phagocytosis of apoptotic neutrophils by monocytes from patients with severe asthma. In conclusion, AT-RvD1 demonstrated both anti-inflammatory and pro-resolution effects in PBMCs from patients with severe asthma and could become in the future an alternative treatment for asthma.
authors.affiliation: Institute of Health Sciences, Department of Clinical Medicine, Laboratory of Experimental Immunopharmacology, Federal University of Triangulo Mineiro, Uberaba, MG, Brazil. Electronic address: erikazambaldi@gmail.com.
authors.forename: Érika Pereira
authors.initials: ÉP
authors.lastname: Zambalde
authors.affiliation: Institute of Health Sciences, Department of Clinical Medicine, Laboratory of Experimental Immunopharmacology, Federal University of Triangulo Mineiro, Uberaba, MG, Brazil. Electronic address: maxellemartins@hotmail.com.
authors.forename: Maxelle Martins
authors.initials: MM
authors.lastname: Teixeira
authors.affiliation: Institute of Health Sciences, Department of Clinical Medicine, Laboratory of Experimental Immunopharmacology, Federal University of Triangulo Mineiro, Uberaba, MG, Brazil. Electronic address: danielyfavarin@hotmail.com.
authors.forename: Daniely Cornelio
authors.initials: DC
authors.lastname: Favarin
authors.affiliation: Institute of Health Sciences, Department of Clinical Medicine, Laboratory of Experimental Immunopharmacology, Federal University of Triangulo Mineiro, Uberaba, MG, Brazil. Electronic address: jhony_sacra@hotmail.com.
authors.forename: Jhony Robison
authors.initials: JR
authors.lastname: de Oliveira
authors.affiliation: Institute of Health Sciences, Department of Clinical Medicine, Laboratory of Experimental Immunopharmacology, Federal University of Triangulo Mineiro, Uberaba, MG, Brazil. Electronic address: mahmagalhaes@gmail.com.
authors.forename: Marcela Lucas
authors.initials: ML
authors.lastname: Magalhães
authors.affiliation: Institute of Health Sciences, Department of Clinical Medicine, Laboratory of Experimental Immunopharmacology, Federal University of Triangulo Mineiro, Uberaba, MG, Brazil. Electronic address: maiaramcunha@yahoo.com.br.
authors.forename: Maiara Medeiros
authors.initials: MM
authors.lastname: Cunha
authors.affiliation: Institute of Health Sciences, Department of Clinical Medicine, Laboratory of Experimental Immunopharmacology, Federal University of Triangulo Mineiro, Uberaba, MG, Brazil. Electronic address: wcsjr@terra.com.br.
authors.forename: Wilson Carneiro
authors.initials: WC
authors.lastname: Silva
authors.affiliation: Inflammation and Pain Laboratory, Department of Pharmacology, School of Medicine of Ribeirao Preto, University of São Paulo, Brazil. Electronic address: cindhana@hotmail.com.
authors.forename: Cindy Hana
authors.initials: CH
authors.lastname: Okuma
authors.affiliation: Laboratory of Immunology, Federal University of Triangulo Mineiro, Uberaba, MG, Brazil. Electronic address: vrodrigues@mednet.com.br.
authors.forename: Virmondes
authors.initials: V
authors.lastname: Rodrigues
authors.affiliation: Pulmonary and Critical Care Medicine Division, Department of Internal Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, United States. Electronic address: blevy@partners.org.
authors.forename: Bruce David
authors.initials: BD
authors.lastname: Levy
authors.affiliation: Institute of Health Sciences, Department of Clinical Medicine, Laboratory of Experimental Immunopharmacology, Federal University of Triangulo Mineiro, Uberaba, MG, Brazil. Electronic address: alexprogerio@biomedicina.uftm.edu.br.
authors.forename: Alexandre de Paula
authors.initials: AP
authors.lastname: Rogerio
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001241:Aspirin / Q000737:chemistry; D001249:Asthma / Q000188:drug therapy* / Q000276:immunology; D002478:Cells, Cultured; D040002:Dermatophagoides pteronyssinus; D004281:Docosahexaenoic Acids / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D016753:Interleukin-10 / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000276:immunology; D051379:Mice; D009504:Neutrophils / Q000187:drug effects* / Q000502:physiology; D010587:Phagocytosis / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; C508609:IL10 protein, human; D014409:Tumor Necrosis Factor-alpha; C518399:resolvin D1; D016753:Interleukin-10; D004281:Docosahexaenoic Acids; D001241:Aspirin
keywords: AT-RvD1; Asthma; Dermatophagoides pteronyssinus; Lipopolysaccharide