title: Evaluation of amniotic mesenchymal cell derivatives on cytokine production in equine alveolar macrophages: an in vitro approach to lung inflammation.
abstract: Data obtained in both animal models and clinical trials suggest that cell-based therapies represent a potential therapeutic strategy for lung repair and remodeling. Recently, new therapeutic approaches based on the use of stem cell derivatives (e.g., conditioned medium (CM) and microvesicles (MVs)) to regenerate tissues and improve their functions were proposed. The aim of this study was to investigate the immunomodulatory effects of equine amniotic mesenchymal cell derivatives on lipopolysaccharide (LPS)-induced cytokine production in equine alveolar macrophages, which may be beneficial in lung inflammatory disorders such as recurrent airway obstruction (RAO) in horses. RAO shares many features with human asthma, including an increased number of cells expressing mRNA for interleukin (IL)-4 and IL-5 and a decreased expression of IFN-γ in bronchoalveolar lavage fluid (BALF) of affected horses.
  
  
  
  The release of TNF-α, IL-6, and TGF-β1 at different time points (1, 24, 48, and 72 h) was measured in equine alveolar macrophages stimulated or not with LPS (10 and 100 ng/mL) in the presence or absence of 10 % CM or 50 × 10(6) MVs/mL. Cytokines were measured using commercially available ELISA kits. For multiple comparisons, analysis of variance was used with Tukey post-hoc test. Differences were considered significant at p ≤ 0.05.
  
  
  
  Significant modulatory effects of CM on LPS-induced TNF-α release at 24 h, and of both CM and MVs on TNF-α release at 48 h were observed. A trend toward a modulatory effect of both CM and MVs on the release of TGF-β and possibly IL-6 was visible over time.
  
  
  
  Results support the potential use of CM and MVs in lung regenerative medicine, especially in situations in which TGF-β may be detrimental, such as respiratory allergy. Further studies should evaluate the potential clinical applications of CM and MVs in equine lung diseases, such as RAO and other inflammatory disorders.
authors.affiliation: Department of Health, Animal Science and Food Safety (VESPA), Università degli Studi di Milano, Via Celoria 10, 20133, Milano, Italy.
authors.forename: Enrica
authors.initials: E
authors.lastname: Zucca
authors.affiliation: Laboratory of Toxicology, DiSFeB, Università degli Studi di Milano, Milan, Italy.
authors.forename: Emanuela
authors.initials: E
authors.lastname: Corsini
authors.affiliation: Laboratory of Toxicology, DiSFeB, Università degli Studi di Milano, Milan, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Galbiati
authors.affiliation: Large Animal Hospital, Reproduction Unit, Università degli Studi di Milano, Lodi, Italy. anna.langeconsiglio@unimi.it.
authors.forename: Anna
authors.initials: A
authors.lastname: Lange-Consiglio
authors.affiliation: Department of Health, Animal Science and Food Safety (VESPA), Università degli Studi di Milano, Via Celoria 10, 20133, Milano, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Ferrucci
mesh_terms: D000650:Amnion / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D000818:Animals; D055252:Cell-Derived Microparticles / Q000737:chemistry / Q000276:immunology; D017077:Culture Media, Conditioned / Q000737:chemistry / Q000494:pharmacology; D005260:Female; D006734:Horse Diseases / Q000276:immunology / Q000473:pathology; D006736:Horses; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000276:immunology; D008070:Lipopolysaccharides / Q000494:pharmacology; D016676:Macrophages, Alveolar / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D008954:Models, Biological; D011014:Pneumonia / Q000276:immunology / Q000473:pathology / Q000662:veterinary; D061251:Primary Cell Culture; D053773:Transforming Growth Factor beta1 / Q000096:biosynthesis* / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000276:immunology
chemical_list: D017077:Culture Media, Conditioned; D015850:Interleukin-6; D008070:Lipopolysaccharides; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha
keywords: Alveolar macrophages; Amniotic mesenchymal cell derivatives; Cytokine; Horse