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Korean J Pediatr 2011 September;54(9) :373-379.
Hu.4-1BB-Fc fusion protein inhibits allergic inflammation and airway hyperresponsiveness in a murine model of asthma
Byoung-Ju Kim (Kim BJ)1, Ji-Won Kwon (Kwon JW)2, Ju-Hee Seo (Seo JH)3, Won-Ah Choi (Choi WA)4, Young-Jun Kim (Kim YJ)4, Mi-Jin Kang (Kang MJ)4, Jinho Yu (Yu Jh)3, Soo-Jong Hong (Hong SJ)3
1Department of Pediatrics, Inje University College of Medicine, Busan, Korea
2Department of Pediatrics, Seoul National University College of Medicine, Seoul, Korea
3Department of Pediatrics, University of Ulsan College of Medicine, Seoul, Korea
4Asan Institute for Life Science, Seoul, Korea
Corresponding Author: Soo-Jong Hong ,Tel: +82-2-3010-3379, Fax: +82-2-473-3725, Email:
Copyright © 2011 by The Korean Pediatric Society
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, IgG1, and IgG2a 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 IgG1 levels and increased serum IgG2a 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.
Keywords: 4-1BB (CD137) | Asthma | Allergic inflammation | Airway hyperresponsiveness | Mouse
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