Background: Lysophosphatidic acid (LPA), a prototypic member of a large family of lysophospholipids, has been recently shown to play a role in immune responses to respiratory diseases. The involvement of LPA in allergic airway inflammation has been reported, but the mechanism remains unclear. Object: We analyzed the biological activity of LPA in vitro and in vivo and investigated its role in allergic inflammation in mice using an LPA receptor 2 (LPA2) antagonist. Methods: We used a murine model with acute allergic inflammation, in which mice are sensitized and challenged with house dust mite, and analyzed airway hyperresponsiveness (AHR), pathological findings, Th2 cytokines, and IL-33 in bronchoalveolar lavage fluid (BALF) and lung homogenates. The effect of LPA on Th2 differentiation and cytokine production was examined in vitro using naive CD4⁺ T cells isolated from splenocytes. We also investigated in vivo the effects of LPA on intranasal administration in mice. Results: The LPA2 antagonist suppressed the increase of AHR, the number of total cells, and eosinophils in BALF and lung tissue. It also decreased the production of IL-13 in BALF and IL-33 and CCL2 in the lung. LPA promoted Th2 cell differentiation and IL-13 production by Th2 cells in vitro. Nasal administration of LPA significantly increased the number of total cells and IL-13 in BALF via regulating the production of IL-33 and CCL-2-derived infiltrating macrophages. Conclusion: These findings suggest that LPA plays an important role in allergic airway inflammation and that the blockade of LPA2 might have therapeutic potential for bronchial asthma.
Int Arch Allergy Immunol

中文翻译：

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溶血磷脂酸调节 Th2 细胞的分化及其拮抗剂抑制过敏性气道炎症。

背景：溶血磷脂酸 (LPA) 是溶血磷脂大家族的原型成员，最近已被证明在呼吸系统疾病的免疫反应中发挥作用。已经报道了 LPA 参与过敏性气道炎症，但机制尚不清楚。目的：我们分析了 LPA 的体外和体内生物活性，并使用 LPA 受体 2 (LPA2) 拮抗剂研究了其在小鼠过敏性炎症中的作用。方法：我们使用了具有急性过敏性炎症的小鼠模型，其中小鼠被屋尘螨致敏和攻击，并分析了气道高反应性 (AHR)、病理结果、Th2 细胞因子和支气管肺泡灌洗液 (BALF) 和肺匀浆中的 IL-33 . LPA 对 Th2 分化和细胞因子产生的影响在体外使用分离自脾细胞的幼稚 CD4 ⁺ T 细胞进行了检测。我们还在体内研究了 LPA 对小鼠鼻内给药的影响。结果：LPA2拮抗剂抑制BALF和肺组织中AHR、总细胞数和嗜酸性粒细胞的增加。它还降低了 BALF 中 IL-13 和肺中 IL-33 和 CCL2 的产生。LPA 在体外促进 Th2 细胞分化和 Th2 细胞产生 IL-13。通过调节 IL-33 和 CCL-2 衍生的浸润巨噬细胞的产生，LPA 的鼻腔给药显着增加了 BALF 中的总细胞数和 IL-13。结论：这些发现表明 LPA 在过敏性气道炎症中起重要作用，并且 LPA2 的阻断可能具有治疗支气管哮喘的潜力。
Int Arch 过敏免疫