Department of Respiratory Medicine, Juntendo University Faculty of Medicine and Graduate School of Medicine, Tokyo, Japan.
Department of Respiratory Medicine, Juntendo University Faculty of Medicine and Graduate School of Medicine, Tokyo, Japan; Research Institute for Diseases of Old Ages, Juntendo University Faculty of Medicine and Graduate School of Medicine, Tokyo, Japan; Atopy (Allergy) Research Center, Juntendo University Faculty of Medicine and Graduate School of Medicine, Tokyo, Japan.
Allergol Int. 2021 Jul;70(3):343-350. doi: 10.1016/j.alit.2020.12.004. Epub 2021 Feb 25.
Previous reports have shown that pathogen-associated patterns (PAMPs) induce the production of interleukin (IL)-1β in macrophages. Moreover, studies using mouse models also suggest that chitin, which acts as a PAMP, induces adjuvant effects and eosinophilic infiltration in the lung. Thus, we investigated the effects of inhaled chitin in mouse models.
We developed mouse models of inhaled chitin particle-induced airway inflammation and steroid-resistant ovalbumin (OVA)-induced airway inflammation. Some experimental groups of mice were treated additionally with dexamethasone (DEX). Murine alveolar macrophages (AMs), which were purified from bronchoalveolar lavage (BAL) fluids, were incubated with chitin, and treated with or without DEX.
The numbers of total cells, AMs, lymphocytes, eosinophils, and neutrophils among BAL-derived cells, as well as the IL-1β levels in BAL fluids and the numbers of IL-1β-positive cells in lung, were significantly increased by chitin stimulation. Airway hyperresponsiveness (AHR) was aggravated in mice of the chitin inflammation model compared to control animals. The production of IL-1β was significantly increased in murine AMs by chitin treatment, but DEX administration did not inhibit this chitin-induced IL-1β production. Furthermore, in mouse models, DEX treatment inhibited the OVA-induced airway inflammation and AHR but not the airway inflammation and AHR induced by chitin or the combination of OVA and chitin.
These results suggest that inhaled chitin induces airway inflammation, AHR, and the production of IL-1β. Furthermore, our findings demonstrate for the first time that inhaled chitin induces steroid-resistant airway inflammation and AHR. Inhaled chitin may contribute to features of steroid-resistant asthma.
先前的报告表明，病原体相关模式（PAMPs）会诱导巨噬细胞产生白细胞介素（IL）-1β。此外，使用小鼠模型的研究还表明，几丁质作为一种 PAMP，可诱导肺部的佐剂效应和嗜酸性粒细胞浸润。因此，我们研究了吸入几丁质对小鼠模型的影响。
我们开发了吸入几丁质颗粒诱导的气道炎症和类固醇耐药卵清蛋白（OVA）诱导的气道炎症的小鼠模型。一些实验组的小鼠还接受了地塞米松（DEX）治疗。从支气管肺泡灌洗液（BAL）中纯化的鼠肺泡巨噬细胞（AMs）与几丁质孵育，并在有或没有 DEX 的情况下进行处理。
BAL 衍生细胞中的总细胞、AMs、淋巴细胞、嗜酸性粒细胞和中性粒细胞的数量，BAL 液中的 IL-1β 水平以及肺中 IL-1β 阳性细胞的数量，均因几丁质刺激而显著增加。与对照动物相比，几丁质炎症模型中的小鼠气道高反应性（AHR）加重。几丁质处理可显著增加鼠 AMs 中 IL-1β 的产生，但 DEX 给药不能抑制这种几丁质诱导的 IL-1β 产生。此外，在小鼠模型中，DEX 治疗抑制了 OVA 诱导的气道炎症和 AHR，但不能抑制几丁质或 OVA 和几丁质联合诱导的气道炎症和 AHR。
这些结果表明，吸入几丁质可引起气道炎症、AHR 和 IL-1β 的产生。此外，我们的研究结果首次表明，吸入几丁质可引起类固醇耐药的气道炎症和 AHR。吸入几丁质可能是导致类固醇耐药性哮喘的特征之一。
