title: AT-RvD1 modulates CCL-2 and CXCL-8 production and NF-κB, STAT-6, SOCS1, and SOCS3 expression on bronchial epithelial cells stimulated with IL-4.
abstract: Bronchial epithelial cells represent the first line of defense against microorganisms and allergens in the airways and play an important role in chronic inflammatory processes such as asthma. In an experimental model, both RvD1 and AT-RvD1, lipid mediators of inflammation resolution, ameliorated some of the most important phenotypes of experimental asthma. Here, we extend these results and demonstrate the effect of AT-RvD1 on bronchial epithelial cells (BEAS-2B) stimulated with IL-4. AT-RvD1 (100 nM) decreased both CCL2 and CXCL-8 production, in part by decreasing STAT6 and NF-κB pathways. Furthermore, the effects of AT-RvD1 were ALX/FRP2 receptor dependent, as the antagonist of this receptor (BOC1) reversed the inhibition of these chemokines by AT-RvD1. In addition, AT-RvD1 decreased SOCS1 and increased SOCS3 expression, which play important roles in Th1 and Th17 modulation, respectively. In conclusion, AT-RvD1 demonstrated significant effects on the IL-4-induced activation of bronchial epithelial cells and consequently the potential to modulate neutrophilic and eosinophilic airway inflammation in asthma. Taken together, these findings identify AT-RvD1 as a potential proresolving therapeutic agent for allergic responses in the airways.
authors.affiliation: Institute of Health Sciences, Department of Clinical Medicine, Laboratory of Experimental Immunopharmacology, Federal University of Triangulo Mineiro, Street Vigário Carlos 162, 38025-350 Uberaba, MG, Brazil.
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, Street Vigário Carlos 162, 38025-350 Uberaba, MG, Brazil.
authors.forename: Daniely Cornélio
authors.initials: DC
authors.lastname: Favarin
authors.affiliation: Institute of Biological and Natural Sciences, Department of Genetics, Federal University of Triangulo Mineiro, Uberaba, MG, Brazil.
authors.forename: Sarah Cristina Sato Vaz
authors.initials: SC
authors.lastname: Tanaka
authors.affiliation: Institute of Biological and Natural Sciences, Department of Genetics, Federal University of Triangulo Mineiro, Uberaba, MG, Brazil.
authors.forename: Marly Aparecida Spadotto
authors.initials: MA
authors.lastname: Balarin
authors.affiliation: Institute of Health Sciences, Department of Clinical Medicine, Federal University of Triangulo Mineiro, Uberaba, MG, Brazil.
authors.forename: David Nascimento Silva
authors.initials: DN
authors.lastname: Teixeira
authors.affiliation: Pulmonary and Critical Care Medicine Division, Department of Internal Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Bruce David
authors.identifier: 0000-0001-9515-5731
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, Street Vigário Carlos 162, 38025-350 Uberaba, MG, Brazil.
authors.forename: Alexandre de Paula
authors.initials: Ade P
authors.lastname: Rogério
mesh_terms: D001249:Asthma / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism; D001980:Bronchi / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism; D002460:Cell Line; D018932:Chemokine CCL2 / Q000096:biosynthesis; D004281:Docosahexaenoic Acids / Q000494:pharmacology*; D004847:Epithelial Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D015847:Interleukin-4 / Q000276:immunology*; D016209:Interleukin-8 / Q000096:biosynthesis; D016328:NF-kappa B / Q000378:metabolism; D050800:STAT6 Transcription Factor / Q000378:metabolism; D000071222:Suppressor of Cytokine Signaling 1 Protein; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics
chemical_list: C111835:CCL2 protein, human; C508606:CXCL8 protein, human; D018932:Chemokine CCL2; D016209:Interleukin-8; D016328:NF-kappa B; C108944:SOCS1 protein, human; C106644:SOCS3 protein, human; D050800:STAT6 Transcription Factor; C494101:STAT6 protein, human; D000071222:Suppressor of Cytokine Signaling 1 Protein; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; C518399:resolvin D1; D015847:Interleukin-4; D004281:Docosahexaenoic Acids