Lipoxin B₄ promotes the resolution of allergic inflammation in the upper and lower airways of mice.
Lipoxin B₄ promotes the resolution of allergic inflammation in the upper and lower airways of mice.
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作者：
慢性粘膜炎症是重要且常见的气道疾病的标志，例如过敏性鼻炎和哮喘。脂氧素 A4 (LXA4) 是一种内源性粘膜炎症促消解介质，可减少过敏和哮喘反应。脂氧素 B4 (LXB4) 是脂氧素家族中结构独特的成员，其信号传导方式与 LXA4 不同。 LXB4 由粘膜组织产生，但其在过敏性炎症中的作用尚不清楚。在这里，我们使用过敏性鼻炎和哮喘的小鼠模型来研究 LXB4 在粘膜炎症中的活性。在上呼吸道，LXB4 显着减少鼻粘膜白细胞以及肥大细胞和嗜酸性粒细胞的脱颗粒。在下气道中，LXB4 显着减少气道炎症、粘液化生和高反应性。 LXB4 对体内肥大细胞脱颗粒的抑制作用比地塞米松更有效，并且这些药物显示出独特的细胞因子调节特性；然而，它们的总体抗炎作用是相当的。 LXB4 降低嗜酸细胞活化趋化因子依赖性嗜酸性粒细胞趋化性、IgE 介导的肥大细胞脱颗粒和 2 型细胞因子受体的表达。总之，这些发现表明 LXB4 具有细胞类型选择性和粘膜保护作用，可扩大脂氧素家族对上呼吸道和下呼吸道疾病的治疗潜力。
Chronic mucosal inflammation is the hallmark of important and common airway diseases, such as allergic rhinitis and asthma. Lipoxin A4 (LXA4) is an endogenous pro-resolving mediator for mucosal inflammation that decreases allergic and asthmatic responses. Lipoxin B4 (LXB4) is a structurally distinct member of the lipoxin family that signals in a manner distinct from LXA4. LXB4 is generated by mucosal tissues, but its actions in allergic inflammation are unknown. Here, we used murine models of allergic rhinitis and asthma to investigate LXB4’s activity in mucosal inflammation. In the upper airway, LXB4 significantly decreased nasal mucosal leukocytes and degranulation of mast cells and eosinophils. In the lower airway, LXB4 significantly decreased airway inflammation, mucus metaplasia and hyper- responsiveness. Inhibition of mast cell degranulation in vivo by LXB4 was more potent than dexamethasone, and these agents displayed unique profiles for cytokine regulation; however, their overall anti-inflammatory actions were comparable. LXB4 decreased eotaxin-dependent eosinophil chemotaxis, IgE-mediated mast cell degranulation and expression of type 2 cytokine receptors. Together, these findings indicate that LXB4 carries cell type selective and mucosal protective actions that broaden the lipoxin family’s therapeutic potential for upper and lower airway catabasis.
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影响因子：
82.9
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Levy, BD;DeSanctis, GT;Serhan, CN
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