Arellano-Orden Elena, Calero-Acuña Carmen, Sánchez-López Verónica, Carrasco-Hernández Laura, Márquez-Martín Eduardo, Ortega-Ruiz Francisco, Otero-Candelera Remedios, Marín-Hinojosa Carmen, López-Campos José Luis
Unidad Médico-Quirúrgica de Enfermedades Respiratorias, Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/Universidad de Sevilla, Seville.
CIBER de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III, Madrid, Spain.
Multidiscip Respir Med. 2022 May 24;17:817. doi: 10.4081/mrm.2022.817. eCollection 2022 Jan 12.
Chronic obstructive pulmonary disease (COPD) is a condition resulting from a persistent inflammatory state in the airways even after smoking cessation. Intriguingly, the reasons behind this persistence of the inflammatory influx without smoking exposure have not been fully unraveled. We aimed to explore the hypothesis that systemic inflammation in COPD patients influences lung cell inflammatory response.
We cultured human lung fibroblast and human airway epithelial cell lines with plasma from COPD patients (four emphysematous-COPD, four asthma-COPD overlap, four chronic bronchitis-COPD, and four bronchiectasis- COPD), and four smokers or ex-smokers without COPD as controls. Non-stimulated cells were used as controls. We measured Interleukine-8 (IL-8), C-reactive protein (CRP) and matrix metalloproteinase-9 (MMP-9) in plasma and culture supernatants by ELISA.
Cells stimulated with plasma from COPD patients and non-COPD smoker subjects produced higher CRP, IL- 8 and MMP-9 levels, an increase for COPD in CRP (p=0.029) in epithelial cells and IL-8 (p=0.039) in fibroblasts and decrease for MMP-9 (p=0.039) in fibroblasts, compared with non-stimulated cells. The response was higher in epithelial cells for IL-8 (p=0.003) and in fibroblasts for MMP-9 (p=0.063). The plasma from chronic bronchitis and bronchiectasis phenotypes induced higher IL-8 in fibroblasts.
Plasma from COPD patients increases the inflammatory response in lung epithelial cells and lung fibroblasts, with a different response depending on the cell type and clinical phenotype.
慢性阻塞性肺疾病(COPD)是一种即使在戒烟后气道仍处于持续炎症状态的疾病。有趣的是,在没有吸烟暴露的情况下炎症持续存在的背后原因尚未完全阐明。我们旨在探讨COPD患者的全身炎症影响肺细胞炎症反应这一假说。
我们用COPD患者(四名肺气肿型COPD患者、四名哮喘-COPD重叠患者、四名慢性支气管炎型COPD患者和四名支气管扩张型COPD患者)的血浆培养人肺成纤维细胞和人气道上皮细胞系,并以四名无COPD的吸烟者或已戒烟者作为对照。未刺激的细胞用作对照。我们通过酶联免疫吸附测定法(ELISA)测量血浆和培养上清液中的白细胞介素-8(IL-8)、C反应蛋白(CRP)和基质金属蛋白酶-9(MMP-9)。
与未刺激的细胞相比,用COPD患者和非COPD吸烟者的血浆刺激的细胞产生更高水平的CRP、IL-8和MMP-9,上皮细胞中COPD患者的CRP升高(p = 0.029),成纤维细胞中IL-8升高(p = 0.039),而成纤维细胞中MMP-9降低(p = 0.039)。上皮细胞中IL-8的反应更高(p = 0.003),成纤维细胞中MMP-9的反应更高(p = 0.063)。慢性支气管炎和支气管扩张型表型的血浆在成纤维细胞中诱导产生更高的IL-8。
COPD患者的血浆增加肺上皮细胞和成纤维细胞中的炎症反应,根据细胞类型和临床表型的不同反应也不同。