Department of Life Science, Pohang University of Science and Technology, Pohang, Gyeongbuk, Korea.
Allergy. 2010 Sep;65(9):1093-103. doi: 10.1111/j.1398-9995.2010.02352.x. Epub 2010 Mar 22.
Allergen-specific T-cell responses orchestrate airway inflammation, which is a characteristic of asthma. Recent evidence suggests that noneosinophilic asthma can be developed by mixed Th1 and Th17 cell responses when exposed to lipopolysaccharide (LPS)-containing allergens.
To evaluate the therapeutic or adverse effects of acetyl salicylic acid (ASA) on the expression of Th1-type and Th17-type inflammation induced by airway exposure to LPS-containing allergens.
Th1 + Th17 asthma and Th2 asthma mouse models were generated by intranasal sensitization with ovalbumin (OVA) and LPS and intraperitoneal sensitization with OVA and alum, respectively. Therapeutic or adverse effects were evaluated after allergen challenge using pharmacologic and transgenic approaches.
Lung infiltration of eosinophils was enhanced in OVA/LPS-sensitized mice by ASA treatment, which was accompanied by the enhanced production of eotaxin. These changes were associated with the down-regulation of Th17 cell response, which was partly dependent on adenosine receptor A1 and A3 subtypes, but up-regulation of allergen-specific IL-13 production from T cells. Lung inflammation induced by LPS-containing allergen was markedly reduced in IL-13-deficient mice in the context of ASA treatment, but not without ASA. Meanwhile, adenosine levels in the lung were enhanced by ASA treatment. Moreover, lung infiltration of eosinophils induced by ASA treatment was reversed by co-treatment of a xanthine oxidase inhibitor (allopurinol).
These findings suggest that ASA changes Th17-type into Th2-type inflammation mainly via the adenosine and uric acid metabolic pathway in the lung.
过敏原特异性 T 细胞反应可调控气道炎症，这是哮喘的特征。最近的证据表明，当接触含有脂多糖（LPS）的变应原时，非嗜酸性粒细胞性哮喘可由混合 Th1 和 Th17 细胞反应发展而来。
评估乙酰水杨酸（ASA）对气道暴露于含 LPS 变应原后诱导的 Th1 型和 Th17 型炎症的治疗或不良反应作用。
通过卵清蛋白（OVA）和 LPS 经鼻内致敏以及 OVA 和 alum 经腹腔致敏分别建立 Th1+Th17 哮喘和 Th2 哮喘小鼠模型。采用药理学和转基因方法在变应原攻击后评估治疗或不良反应作用。
ASA 处理增强了 OVA/LPS 致敏小鼠肺内嗜酸性粒细胞浸润，同时伴有嗜酸性粒细胞趋化因子 eotaxin 的产生增加。这些变化与 Th17 细胞反应的下调有关，部分依赖于腺苷受体 A1 和 A3 亚型，但与 T 细胞中过敏原特异性 IL-13 产生的上调有关。在 ASA 治疗的情况下，IL-13 缺陷小鼠的含 LPS 变应原诱导的肺炎症明显减轻，但没有 ASA 则不然。同时，ASA 处理增强了肺内的腺苷水平。此外，ASA 处理诱导的嗜酸性粒细胞浸润可通过黄嘌呤氧化酶抑制剂（别嘌呤醇）的共同治疗而逆转。
这些发现表明，ASA 通过肺内的腺苷和尿酸代谢途径将 Th17 型转化为 Th2 型炎症，主要通过肺内的腺苷和尿酸代谢途径。
