Department of Pathophysiology, National Koranyi Institute of Pulmonology, Budapest, Hungary.
Department of Pulmonology, National Koranyi Institute of Pulmonology, Budapest, Hungary.
Int J Chron Obstruct Pulmon Dis. 2022 Aug 19;17:1897-1908. doi: 10.2147/COPD.S364982. eCollection 2022.
Cytokines are extracellular signaling proteins that have been widely implicated in the pathogenesis of chronic obstructive pulmonary disease (COPD). Here, we investigated cytokine expression both at the mRNA and protein level in the sputum of healthy individuals, stable COPD patients, and those experiencing a severe acute exacerbation (AECOPD) requiring hospitalization.
Sputum was collected in 19 healthy controls, 25 clinically stable COPD patients, and 31 patients with AECOPD. In AECOPD patients sample collection was performed both at the time of hospital admission and at discharge following treatment. Sputum supernatant was analyzed by an antibody microarray detecting 120 cytokines simultaneously, while the mRNA expression of 14 selected cytokines in sputum cells was investigated by real-time PCR (qPCR).
Proteomic analysis identified interleukin (IL)-6 and growth-regulated oncogene (GRO)α as the only sputum cytokines that were differentially expressed between stable COPD patients and healthy controls. At the onset of AECOPD, several cytokines exhibited altered sputum expression compared to stable COPD. Recovery from AECOPD induced significant changes in the sputum cytokine protein profile; however, the length of hospitalization was insufficient for most cytokines to return to stable levels. With regard to gene expression analysis by qPCR, we found that bone morphogenetic protein (BMP)-4 was up-regulated, while IL-1α, monokine-induced by interferon-γ (MIG), and BMP-6 were down-regulated at the mRNA level in patients with AECOPD compared to stable disease.
The sputum cytokine signature of AECOPD differs from that of stable COPD. Protein level changes are asynchronous with changes in gene expression at the mRNA level in AECOPD. The observation that the levels of most cytokines do not stabilize with acute treatment of AECOPD suggests a prolonged effect of exacerbation on the status of COPD patients.
细胞因子是细胞外信号蛋白，它们广泛参与慢性阻塞性肺疾病（COPD）的发病机制。在这里，我们研究了健康个体、稳定期 COPD 患者和需要住院治疗的严重急性加重（AECOPD）患者的痰液中细胞因子的 mRNA 和蛋白水平表达。
收集了 19 名健康对照者、25 名临床稳定的 COPD 患者和 31 名 AECOPD 患者的痰液。在 AECOPD 患者中，在入院时和治疗后出院时分别进行了样本采集。使用抗体微阵列分析痰液上清液，同时通过实时 PCR（qPCR）检测 14 种选定细胞因子在痰液细胞中的 mRNA 表达。
蛋白质组学分析确定白细胞介素（IL）-6 和生长调节癌基因（GRO）α是稳定期 COPD 患者和健康对照者之间痰液细胞因子差异表达的唯一两种细胞因子。在 AECOPD 发作时，与稳定期 COPD 相比，几种细胞因子的痰液表达发生了改变。AECOPD 恢复后，痰液细胞因子蛋白谱发生了显著变化；然而，住院时间不足以使大多数细胞因子恢复到稳定水平。通过 qPCR 进行基因表达分析，我们发现与稳定疾病相比，AECOPD 患者的骨形态发生蛋白（BMP）-4 上调，而白细胞介素-1α（IL-1α）、干扰素-γ诱导的单核细胞趋化蛋白（MIG）和 BMP-6 下调。
AECOPD 的痰液细胞因子特征与稳定期 COPD 不同。AECOPD 中蛋白水平的变化与 mRNA 水平的基因表达变化不同步。AECOPD 急性治疗后大多数细胞因子水平不稳定的观察结果表明，急性加重对 COPD 患者的状态有长期影响。
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