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

다국어 초록 (Multilingual 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, 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 IgG1 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.

참고문헌 (Reference)

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