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Lobeglitazone Attenuates Airway Inflammation and Mucus Hypersecretion in a Murine Model of Ovalbumin-Induced Asthma
Lobeglitazone (LB) is a novel agonist of peroxisome proliferator-activated receptor (PPAR)-α and γ that was developed as a drug to treat diabetes mellitus. We explored the ameliorative effects of LB on allergic asthma using a murine model of ovalbumin (OVA)-induced asthma. To boost the immune respon...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6092601/ https://www.ncbi.nlm.nih.gov/pubmed/30135657 http://dx.doi.org/10.3389/fphar.2018.00906 |
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author | Shin, Na-Rae Park, Sung-Hyeuk Ko, Je-Won Cho, Young-Kwon Lee, In-Chul Kim, Jong-Choon Shin, In-Sik Kim, Joong-Sun |
author_facet | Shin, Na-Rae Park, Sung-Hyeuk Ko, Je-Won Cho, Young-Kwon Lee, In-Chul Kim, Jong-Choon Shin, In-Sik Kim, Joong-Sun |
author_sort | Shin, Na-Rae |
collection | PubMed |
description | Lobeglitazone (LB) is a novel agonist of peroxisome proliferator-activated receptor (PPAR)-α and γ that was developed as a drug to treat diabetes mellitus. We explored the ameliorative effects of LB on allergic asthma using a murine model of ovalbumin (OVA)-induced asthma. To boost the immune response of animals, OVA sensitization was performed on days 0 and 14. LB (250 or 500 μg/kg) was administered by oral gavage on days 18 to 23, and the OVA challenge was performed using an ultrasonic nebulizer on days 21 to 23. Plethysmography showed airway hyperresponsiveness (AHR) on day 24. LB treatment effectively decreased inflammatory cell recruitment, T-helper type 2 cytokines in the bronchoalveolar lavage fluid, and immunoglobulin (Ig) E in the serum of the animals with OVA-induced asthma, which was accompanied by a marked reduction in AHR. It also decreased airway inflammation, mucus hypersecretion, phosphorylation of nuclear transcription factor-kappa-B (NF-κB), and expression of activating protein (AP)-1 and mucin 5AC (MUC5AC). Overall, LB effectively attenuated the pathophysiological changes of asthma and its effects appear related to a reduction in the phosphorylation of NF-κB and the expression of AP-1. Thus, our results suggest that LB has a potential to treat allergic asthma. |
format | Online Article Text |
id | pubmed-6092601 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-60926012018-08-22 Lobeglitazone Attenuates Airway Inflammation and Mucus Hypersecretion in a Murine Model of Ovalbumin-Induced Asthma Shin, Na-Rae Park, Sung-Hyeuk Ko, Je-Won Cho, Young-Kwon Lee, In-Chul Kim, Jong-Choon Shin, In-Sik Kim, Joong-Sun Front Pharmacol Pharmacology Lobeglitazone (LB) is a novel agonist of peroxisome proliferator-activated receptor (PPAR)-α and γ that was developed as a drug to treat diabetes mellitus. We explored the ameliorative effects of LB on allergic asthma using a murine model of ovalbumin (OVA)-induced asthma. To boost the immune response of animals, OVA sensitization was performed on days 0 and 14. LB (250 or 500 μg/kg) was administered by oral gavage on days 18 to 23, and the OVA challenge was performed using an ultrasonic nebulizer on days 21 to 23. Plethysmography showed airway hyperresponsiveness (AHR) on day 24. LB treatment effectively decreased inflammatory cell recruitment, T-helper type 2 cytokines in the bronchoalveolar lavage fluid, and immunoglobulin (Ig) E in the serum of the animals with OVA-induced asthma, which was accompanied by a marked reduction in AHR. It also decreased airway inflammation, mucus hypersecretion, phosphorylation of nuclear transcription factor-kappa-B (NF-κB), and expression of activating protein (AP)-1 and mucin 5AC (MUC5AC). Overall, LB effectively attenuated the pathophysiological changes of asthma and its effects appear related to a reduction in the phosphorylation of NF-κB and the expression of AP-1. Thus, our results suggest that LB has a potential to treat allergic asthma. Frontiers Media S.A. 2018-08-08 /pmc/articles/PMC6092601/ /pubmed/30135657 http://dx.doi.org/10.3389/fphar.2018.00906 Text en Copyright © 2018 Shin, Park, Ko, Cho, Lee, Kim, Shin and Kim. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Pharmacology Shin, Na-Rae Park, Sung-Hyeuk Ko, Je-Won Cho, Young-Kwon Lee, In-Chul Kim, Jong-Choon Shin, In-Sik Kim, Joong-Sun Lobeglitazone Attenuates Airway Inflammation and Mucus Hypersecretion in a Murine Model of Ovalbumin-Induced Asthma |
title | Lobeglitazone Attenuates Airway Inflammation and Mucus Hypersecretion in a Murine Model of Ovalbumin-Induced Asthma |
title_full | Lobeglitazone Attenuates Airway Inflammation and Mucus Hypersecretion in a Murine Model of Ovalbumin-Induced Asthma |
title_fullStr | Lobeglitazone Attenuates Airway Inflammation and Mucus Hypersecretion in a Murine Model of Ovalbumin-Induced Asthma |
title_full_unstemmed | Lobeglitazone Attenuates Airway Inflammation and Mucus Hypersecretion in a Murine Model of Ovalbumin-Induced Asthma |
title_short | Lobeglitazone Attenuates Airway Inflammation and Mucus Hypersecretion in a Murine Model of Ovalbumin-Induced Asthma |
title_sort | lobeglitazone attenuates airway inflammation and mucus hypersecretion in a murine model of ovalbumin-induced asthma |
topic | Pharmacology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6092601/ https://www.ncbi.nlm.nih.gov/pubmed/30135657 http://dx.doi.org/10.3389/fphar.2018.00906 |
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