Divisione di Pneumologia e Laboratorio di Citoimmunopatologia dell'Apparato Cardio Respiratorio, Fondazione Salvatore Maugeri, IRCCS, Veruno (NO) e Tradate, Pavia, Italy.
Centro Interdipartimentale per lo Studio delle Malattie Infiammatorie delle Vie Aeree e Patologie Fumo-correlate (CEMICEF; formerly Centro di Ricerca su Asma e BPCO), Sezione di Medicina Interna e Cardiorespiratoria (formerly Sezione di Malattie dell'Apparato Respiratorio), Università di Ferrara, Ferrara, Italy.
Thorax. 2014 Jun;69(6):516-24. doi: 10.1136/thoraxjnl-2012-203062. Epub 2014 Jan 15.
In models of COPD, environmental stressors induce innate immune responses, inflammasome activation and inflammation. However, the interaction between these responses and their role in driving pulmonary inflammation in stable COPD is unknown.
To investigate the activation of innate immunity and inflammasome pathways in the bronchial mucosa and bronchoalveolar lavage (BAL) of patients with stable COPD of different severity and control healthy smokers and non-smokers.
Innate immune mediators (interleukin (IL)-6, IL-7, IL-10, IL-27, IL-37, thymic stromal lymphopoietin (TSLP), interferon γ and their receptors, STAT1 and pSTAT1) and inflammasome components (NLRP3, NALP7, caspase 1, IL-1β and its receptors, IL-18, IL-33, ST2) were measured in the bronchial mucosa using immunohistochemistry. IL-6, soluble IL-6R, sgp130, IL-7, IL-27, HMGB1, IL-33, IL-37 and soluble ST2 were measured in BAL using ELISA.
In bronchial biopsies IL-27+ and pSTAT1+ cells are increased in patients with severe COPD compared with control healthy smokers. IL-7+ cells are increased in patients with COPD and control smokers compared with control non-smokers. In severe stable COPD IL-7R+, IL-27R+ and TSLPR+ cells are increased in comparison with both control groups. The NALP3 inflammasome is not activated in patients with stable COPD compared with control subjects. The inflammasome inhibitory molecules NALP7 and IL-37 are increased in patients with COPD compared with control smokers. IL-6 levels are increased in BAL from patients with stable COPD compared with control smokers with normal lung function whereas IL-1β and IL-18 were similar across all groups.
Increased expression of IL-27, IL-37 and NALP7 in the bronchial mucosa may be involved in progression of stable COPD.
在 COPD 模型中，环境应激源会引起先天免疫反应、炎性体激活和炎症。然而，这些反应之间的相互作用及其在驱动稳定 COPD 中肺部炎症的作用尚不清楚。
研究不同严重程度稳定 COPD 患者、健康吸烟者和非吸烟者支气管黏膜和支气管肺泡灌洗液（BAL）中先天免疫和炎性体途径的激活情况。
采用免疫组织化学法检测支气管黏膜中先天免疫介质（白细胞介素（IL）-6、IL-7、IL-10、IL-27、IL-37、胸腺基质淋巴生成素（TSLP）、干扰素γ及其受体、STAT1 和 pSTAT1）和炎性体成分（NLRP3、NALP7、半胱天冬酶 1、IL-1β及其受体、IL-18、IL-33、ST2）。采用 ELISA 法检测 BAL 中 IL-6、可溶性 IL-6R、sgp130、IL-7、IL-27、HMGB1、IL-33、IL-37 和可溶性 ST2。
在支气管活检中，与健康吸烟者相比，严重 COPD 患者的 IL-27+和 pSTAT1+细胞增加。与非吸烟者相比，COPD 患者和健康吸烟者的 IL-7+细胞增加。与两组对照相比，严重稳定 COPD 患者的 IL-7R+、IL-27R+和 TSLPR+细胞增加。与对照组相比，稳定 COPD 患者的 NALP3 炎性体未被激活。与健康吸烟者相比，COPD 患者的炎性体抑制分子 NALP7 和 IL-37 增加。与健康吸烟者（肺功能正常）相比，稳定 COPD 患者的 BAL 中 IL-6 水平升高，而 IL-1β和 IL-18 在所有组之间相似。
支气管黏膜中 IL-27、IL-37 和 NALP7 的表达增加可能与稳定 COPD 的进展有关。
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