Cheng Wun-Hao, Zhuang Ting-Li, Lee Meng-Jung, Chou Chun-Liang, Chen Bing-Chang, Kuo Han-Pin, Weng Chih-Ming
School of Respiratory Therapy, Taipei Medical University College of Medicine, 250 Wu-Hsing Street, Taipei, 11031, Taiwan.
Respiratory Therapy, Division of Pulmonary Medicine, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan.
Mol Med. 2024 Dec 20;30(1):262. doi: 10.1186/s10020-024-01035-y.
Mast cells are implicated in the pathogenesis and severity of asthma in children and adults. The release of proinflammatory mediators and cytokines from activated mast cells (MC) is associated with Type 2 (T2) cell-skewed inflammation.
We obtained the airway tissues of Balb/c mice with or without intra-tracheal diesel exhaust particles (DEP) instillation to measure the extent of tryptase MCs infiltration and interleukin (IL)-33 expression. Cultured human mast cells (HMC-1) were stimulated with DEP to determine the role of aryl hydrocarbon receptor (AhR) in mediating the synthesis and release of IL-33 and type-2 cytokines.
In the control animals, most of the MC accumulated in the submucosal vessels without expression of IL-33. Intra-tracheal DEP installation increased the number of IL-33MC infiltrating in the epithelial and sub-epithelial areas of mice. Human MC exposed to DEP upregulated mRNA and protein expression of IL-33. These effects were abolished by knockdown of expression of the AhR or AhR nuclear translocator (ARNT) by small interfering (si)RNA transfection. DEP also activated nuclear factor-kappa B (NF-κB) to facilitate nuclear translocation of the AhR. DEP increased MC migration and induced the synthesis and release of IL-4, IL-5, and IL-13 in MCs, and these effects were abolished by anti-ST2 antibodies.
Airborne pollutants may activate MCs to produce IL-33 via the AhR/NF-κB pathway, leading to type 2 cytokines production and enhancing MC airway epithelium-shifted migration through the autocrine or paracrine IL-33/ST2 axis.
肥大细胞与儿童和成人哮喘的发病机制及严重程度有关。活化的肥大细胞（MC）释放促炎介质和细胞因子与2型（T2）细胞偏向性炎症相关。
我们获取了经气管内滴注柴油废气颗粒（DEP）或未滴注的Balb/c小鼠的气道组织，以测量类胰蛋白酶MC浸润程度和白细胞介素（IL）-33表达。用DEP刺激培养的人肥大细胞（HMC-1），以确定芳烃受体（AhR）在介导IL-33和2型细胞因子合成与释放中的作用。
在对照动物中，大多数MC积聚在黏膜下血管中，无IL-33表达。气管内滴注DEP增加了浸润于小鼠上皮和上皮下区域的IL-33⁺MC数量。暴露于DEP的人MC上调了IL-33的mRNA和蛋白表达。通过小干扰（si）RNA转染敲低AhR或AhR核转运蛋白（ARNT）的表达可消除这些效应。DEP还激活核因子-κB（NF-κB）以促进AhR的核转位。DEP增加了MC迁移，并诱导MC合成和释放IL-4、IL-5和IL-13，而抗ST2抗体可消除这些效应。
空气传播污染物可能通过AhR/NF-κB途径激活MC产生IL-33，导致2型细胞因子产生，并通过自分泌或旁分泌IL-33/ST2轴增强MC向气道上皮的迁移。
