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Hu.4-1BB-Fc fusion protein inhibits allergic inflammation and airway hyperresponsiveness in a murine model of asthma

PURPOSE: 4-1BB (CD 137) is a costimulatory molecule expressed on activated T-cells. Repression by 4-1BB is thought to attenuate Th2-mediated allergic reactions. The aim of this study was to investigate the effect of 4-1BB on allergic airway inflammation in a murine asthma model. METHODS: BALB/c mice...

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Autores principales: Kim, Byoung-Ju, Kwon, Ji-Won, Seo, Ju-Hee, Choi, Won-Ah, Kim, Young-Jun, Kang, Mi-Jin, Yu, Jinho, Hong, Soo-Jong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Korean Pediatric Society 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3250603/
https://www.ncbi.nlm.nih.gov/pubmed/22232630
http://dx.doi.org/10.3345/kjp.2011.54.9.373
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author Kim, Byoung-Ju
Kwon, Ji-Won
Seo, Ju-Hee
Choi, Won-Ah
Kim, Young-Jun
Kang, Mi-Jin
Yu, Jinho
Hong, Soo-Jong
author_facet Kim, Byoung-Ju
Kwon, Ji-Won
Seo, Ju-Hee
Choi, Won-Ah
Kim, Young-Jun
Kang, Mi-Jin
Yu, Jinho
Hong, Soo-Jong
author_sort Kim, Byoung-Ju
collection PubMed
description PURPOSE: 4-1BB (CD 137) is a costimulatory molecule expressed on activated T-cells. Repression by 4-1BB is thought to attenuate Th2-mediated allergic reactions. The aim of this study was to investigate the effect of 4-1BB on allergic airway inflammation in a murine asthma model. METHODS: BALB/c mice were sensitized to and challenged with ovalbumin (OVA). Hu.4-1BB-Fc was administered 1 day before the first OVA sensitization or 1 day after the second OVA sensitization. Following antigen challenge, airway responsiveness to methacholine was assessed and bronchoalveolar lavage (BAL) fluid was analyzed. Total immunoglobulin (Ig) E, OVA-specific IgE, IgG(1), and IgG(2a) levels in sera were measured by enzyme-linked immunosorbent assay. Lung pathology was also evaluated. RESULTS: In mice treated with Hu.4-1BB-Fc before the first OVA sensitization, there was a marked decrease in airway hyperresponsiveness, total cell count, and eosinophil count in the BAL fluid. In addition, Hu.4-1BB-Fc treatment decreased serum OVA-specific IgG(1) levels and increased serum IgG(2a) level significantly compared with the corresponding levels in mice sensitized to and challenged with OVA. Hu.4-1BB-Fc-treated mice also showed suppressed peribronchial and perivascular inflammatory cell infiltration. In contrast, treatment with Hu.4-1BB-Fc 1 day after sensitization had no effect on airway hyperresponsiveness and showed less suppression of inflammation in lung tissue. CONCLUSION: Administration of Hu.4-1BB-Fc can attenuate airway inflammation and hyperreactivity in a mouse model of allergic airway inflammation. In addition, administration before sensitization may be more effective. These findings suggest that 4-1BB may be a useful therapeutic molecule against asthma.
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spelling pubmed-32506032012-01-09 Hu.4-1BB-Fc fusion protein inhibits allergic inflammation and airway hyperresponsiveness in a murine model of asthma Kim, Byoung-Ju Kwon, Ji-Won Seo, Ju-Hee Choi, Won-Ah Kim, Young-Jun Kang, Mi-Jin Yu, Jinho Hong, Soo-Jong Korean J Pediatr Original Article PURPOSE: 4-1BB (CD 137) is a costimulatory molecule expressed on activated T-cells. Repression by 4-1BB is thought to attenuate Th2-mediated allergic reactions. The aim of this study was to investigate the effect of 4-1BB on allergic airway inflammation in a murine asthma model. METHODS: BALB/c mice were sensitized to and challenged with ovalbumin (OVA). Hu.4-1BB-Fc was administered 1 day before the first OVA sensitization or 1 day after the second OVA sensitization. Following antigen challenge, airway responsiveness to methacholine was assessed and bronchoalveolar lavage (BAL) fluid was analyzed. Total immunoglobulin (Ig) E, OVA-specific IgE, IgG(1), and IgG(2a) levels in sera were measured by enzyme-linked immunosorbent assay. Lung pathology was also evaluated. RESULTS: In mice treated with Hu.4-1BB-Fc before the first OVA sensitization, there was a marked decrease in airway hyperresponsiveness, total cell count, and eosinophil count in the BAL fluid. In addition, Hu.4-1BB-Fc treatment decreased serum OVA-specific IgG(1) levels and increased serum IgG(2a) level significantly compared with the corresponding levels in mice sensitized to and challenged with OVA. Hu.4-1BB-Fc-treated mice also showed suppressed peribronchial and perivascular inflammatory cell infiltration. In contrast, treatment with Hu.4-1BB-Fc 1 day after sensitization had no effect on airway hyperresponsiveness and showed less suppression of inflammation in lung tissue. CONCLUSION: Administration of Hu.4-1BB-Fc can attenuate airway inflammation and hyperreactivity in a mouse model of allergic airway inflammation. In addition, administration before sensitization may be more effective. These findings suggest that 4-1BB may be a useful therapeutic molecule against asthma. The Korean Pediatric Society 2011-09 2011-09-30 /pmc/articles/PMC3250603/ /pubmed/22232630 http://dx.doi.org/10.3345/kjp.2011.54.9.373 Text en Copyright © 2011 by The Korean Pediatric Society http://creativecommons.org/licenses/by-nc/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Article
Kim, Byoung-Ju
Kwon, Ji-Won
Seo, Ju-Hee
Choi, Won-Ah
Kim, Young-Jun
Kang, Mi-Jin
Yu, Jinho
Hong, Soo-Jong
Hu.4-1BB-Fc fusion protein inhibits allergic inflammation and airway hyperresponsiveness in a murine model of asthma
title Hu.4-1BB-Fc fusion protein inhibits allergic inflammation and airway hyperresponsiveness in a murine model of asthma
title_full Hu.4-1BB-Fc fusion protein inhibits allergic inflammation and airway hyperresponsiveness in a murine model of asthma
title_fullStr Hu.4-1BB-Fc fusion protein inhibits allergic inflammation and airway hyperresponsiveness in a murine model of asthma
title_full_unstemmed Hu.4-1BB-Fc fusion protein inhibits allergic inflammation and airway hyperresponsiveness in a murine model of asthma
title_short Hu.4-1BB-Fc fusion protein inhibits allergic inflammation and airway hyperresponsiveness in a murine model of asthma
title_sort hu.4-1bb-fc fusion protein inhibits allergic inflammation and airway hyperresponsiveness in a murine model of asthma
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3250603/
https://www.ncbi.nlm.nih.gov/pubmed/22232630
http://dx.doi.org/10.3345/kjp.2011.54.9.373
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