Hu.4-1BB-Fc fusion protein inhibits allergic inflammation and airway hyperresponsiveness in a murine model of asthma.
10.3345/kjp.2011.54.9.373
- Author:
Byoung Ju KIM
1
;
Ji Won KWON
;
Ju Hee SEO
;
Won Ah CHOI
;
Young Jun KIM
;
Mi Jin KANG
;
Jinho YU
;
Soo Jong HONG
Author Information
1. Department of Pediatrics, Inje University College of Medicine, Busan, Korea.
- Publication Type:Original Article
- Keywords:
4-1BB (CD137);
Asthma;
Allergic inflammation;
Airway hyperresponsiveness;
Mouse
- MeSH:
Animals;
Asthma;
Bronchoalveolar Lavage;
Cell Count;
Enzyme-Linked Immunosorbent Assay;
Eosinophils;
Hypersensitivity;
Immunoglobulin E;
Immunoglobulin G;
Immunoglobulins;
Inflammation;
Lung;
Methacholine Chloride;
Mice;
Ovalbumin;
Ovum;
Repression, Psychology;
T-Lymphocytes
- From:Korean Journal of Pediatrics
2011;54(9):373-379
- CountryRepublic of Korea
- Language:English
-
Abstract:
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.
