The anti-allergic effect and the underlying mechanism of sodium 4-phenylbutyrate in ovalbumin-induced asthmatic mice

• Main Authors: Jia-Ling Lu, 盧珈伶
• Other Authors: 李岳倫
• Format: Others
• Language: zh-TW
• Published: 2014
• Online Access: http://ndltd.ncl.edu.tw/handle/9xg3n8

碩士 === 臺北醫學大學 === 醫學科學研究所 === 102 === Atopic asthma is a chronic inflammatory disease of the airways induced by type 2 T helper cell (Th2) immune response. It is characterized by airway eosinophilia, goblet cell hyperplasia with mucus hypersecretion and hyper-responsiveness in response to allergens. Short-chain fatty acids (SCFAs) have anti-inflammatory and immune-suppressive properties and are considered good candidates to inhibit allergen-induced disorders. In this study, we aim to investigate the anti-allergic ability and regulatory mechanisms of SCFAs on asthma. Firstly, we assessed the immunomodulatory effects of these SCFAs on the activation and function of bone marrow-derived dendritic cells (DCs) and CD4+ T cells in vitro. Our data showed that SCFAs, sodium butyrate (NaB) and sodium phenylbutyrate (NaPB), inhibited the secretion of TNF-α, IL-10 and IL-12 in LPS-stimulated DCs. Besides, the expression of surface makers on DCs was also reduced upon NaB or NaPB treatment. Thus, we proposed that NaB and NaPB might impair DCs’ maturation and activation and further affect T cell response. By co-culturing irradiated DCs with CD4+ T cells, we found that NaPB-treated DCs could inhibit the proliferation of CD4+ T cells. Additionally, we found that NaPB could directly suppress anti-CD3/CD28 antibodies-activated CD4+ T cell proliferation and cytokine production. On the other hand, DO11.10 splenocytes were cultured with NaPB in the presence of OVA and the effects on cytokine release were assessed. NaPB treatment suppressed IL-5 and IL-13 release, but had positive effect on IL-10 and IFN-γ production. Base on the above results, we thought that NaPB may have the ability to modulate allergic-specific immune responses in vivo. Finally, a murine model of OVA-induced asthma was used to investigate the preventative effect of anti-allergic effect of NaPB in these mice. Our data showed that NaPB-treated mice expressed lower levels of serum IgE and IgG1 than control mice. Besides, the development of airway hyper-responsiveness and the infiltration of eosinophils in lungs were alleviated by NaPB treatment. Notably, the secretion of Th2 cytokines was decreased but the production of IL-10 and IFN-γ was markedly increased in NaPB-treated mice. NaPB also enhanced the generation of Foxp3+CD4+ regulatory T cells inthese mice. Taken together, these results indicate that NaPB acts as anti-allergic regulator on immune effector cells and exerts preventative effects on OVA-induced asthma in mice.a In the future, we hope that NaPB can be developed as a novel agent to treat allergic diseases.