TY - JOUR
T1 - Eicosapentaenoic acid enhances the effects of mesenchymal Stromal cell therapy in experimental allergic asthma
AU - Abreu, Soraia Carvalho
AU - Lopes-Pacheco, Miquéias
AU - Silva, Adriana Lopes da
AU - Xisto, Debora Gonçalves
AU - Oliveira, Tainá Batista de
AU - Kitoko, Jamil Zola
AU - Castro, Lígia Lins de
AU - Amorim, Natália Recardo
AU - Martins, Vanessa
AU - Silva, Luisa H.A.
AU - Gonçalves-de-Albuquerque, Cassiano Felippe
AU - Faria-Neto, Hugo Caire de Castro
AU - Olsen, Priscilla Christina
AU - Weiss, Daniel Jay
AU - Morales, Marcelo Marcos
AU - Diaz, Bruno Lourenço
AU - Rocco, Patricia Rieken Macêdo
N1 - Publisher Copyright:
© 2018 Abreu, Lopes-Pacheco, da Silva, Xisto, de Oliveira, Kitoko, de Castro, Amorim, Martins, Silva, Gonçalves-de-Albuquerque, Castro Faria-Neto, Olsen, Weiss, Morales, Diaz and Rocco.
PY - 2018/5/24
Y1 - 2018/5/24
N2 - Asthma is characterized by chronic lung inflammation and airway hyperresponsiveness. Despite recent advances in the understanding of its pathophysiology, asthma remains a major public health problem and, at present, there are no effective interventions capable of reversing airway remodeling. Mesenchymal stromal cell (MSC)-based therapy mitigates lung inflammation in experimental allergic asthma; however, its ability to reduce airway remodeling is limited. We aimed to investigate whether pre-treatment with eicosapentaenoic acid (EPA) potentiates the therapeutic properties of MSCs in experimental allergic asthma. Seventy-two C57BL/6 mice were used. House dust mite (HDM) extract was intranasally administered to induce severe allergic asthma in mice. Unstimulated or EPA-stimulated MSCs were administered intratracheally 24 h after final HDM challenge. Lung mechanics, histology, protein levels of biomarkers, and cellularity in bronchoalveolar lavage fluid (BALF), thymus, lymph nodes, and bone marrow were analyzed. Furthermore, the effects of EPA on lipid body formation and secretion of resolvin-D1 (RvD1), prostaglandin E2 (PGE2), interleukin (IL)-10, and transforming growth factor (TGF)-β1 by MSCs were evaluated in vitro. EPA-stimulated MSCs, compared to unstimulated MSCs, yielded greater therapeutic effects by further reducing bronchoconstriction, alveolar collapse, total cell counts (in BALF, bone marrow, and lymph nodes), and collagen fiber content in airways, while increasing IL-10 levels in BALF and M2 macrophage counts in lungs. In conclusion, EPA potentiated MSC-based therapy in experimental allergic asthma, leading to increased secretion of pro-resolution and anti-inflammatory mediators (RvD1, PGE2, IL-10, and TGF-β), modulation of macrophages toward an anti-inflammatory phenotype, and reduction in the remodeling process. Taken together, these modifications may explain the greater improvement in lung mechanics obtained. This may be a promising novel strategy to potentiate MSCs effects.
AB - Asthma is characterized by chronic lung inflammation and airway hyperresponsiveness. Despite recent advances in the understanding of its pathophysiology, asthma remains a major public health problem and, at present, there are no effective interventions capable of reversing airway remodeling. Mesenchymal stromal cell (MSC)-based therapy mitigates lung inflammation in experimental allergic asthma; however, its ability to reduce airway remodeling is limited. We aimed to investigate whether pre-treatment with eicosapentaenoic acid (EPA) potentiates the therapeutic properties of MSCs in experimental allergic asthma. Seventy-two C57BL/6 mice were used. House dust mite (HDM) extract was intranasally administered to induce severe allergic asthma in mice. Unstimulated or EPA-stimulated MSCs were administered intratracheally 24 h after final HDM challenge. Lung mechanics, histology, protein levels of biomarkers, and cellularity in bronchoalveolar lavage fluid (BALF), thymus, lymph nodes, and bone marrow were analyzed. Furthermore, the effects of EPA on lipid body formation and secretion of resolvin-D1 (RvD1), prostaglandin E2 (PGE2), interleukin (IL)-10, and transforming growth factor (TGF)-β1 by MSCs were evaluated in vitro. EPA-stimulated MSCs, compared to unstimulated MSCs, yielded greater therapeutic effects by further reducing bronchoconstriction, alveolar collapse, total cell counts (in BALF, bone marrow, and lymph nodes), and collagen fiber content in airways, while increasing IL-10 levels in BALF and M2 macrophage counts in lungs. In conclusion, EPA potentiated MSC-based therapy in experimental allergic asthma, leading to increased secretion of pro-resolution and anti-inflammatory mediators (RvD1, PGE2, IL-10, and TGF-β), modulation of macrophages toward an anti-inflammatory phenotype, and reduction in the remodeling process. Taken together, these modifications may explain the greater improvement in lung mechanics obtained. This may be a promising novel strategy to potentiate MSCs effects.
KW - Histology
KW - Inflammation
KW - Lung mechanics
KW - Remodeling
KW - Resolvin
UR - http://www.scopus.com/inward/record.url?scp=85047470450&partnerID=8YFLogxK
U2 - 10.3389/fimmu.2018.01147
DO - 10.3389/fimmu.2018.01147
M3 - Artículo
AN - SCOPUS:85047470450
SN - 1664-3224
VL - 9
JO - Frontiers in Immunology
JF - Frontiers in Immunology
IS - MAY
M1 - 1147
ER -
