Dessalle K, Narayanan V, Kyoh S, Mogas A, Halayko A J, Nair P, Baglole C J, Eidelman D H, Ludwig M S, Hamid Q
Meakins-Christie Laboratories, McGill University, Montreal, QC, Canada.
Faculty of Medicine, University of Manitoba, Winnipeg, MB, Canada.
Clin Exp Allergy. 2016 Jul;46(7):945-56. doi: 10.1111/cea.12744. Epub 2016 May 15.
Chronic inflammation, typified by increased expression of IL-17A, together with airway and parenchymal remodelling are features of chronic lung diseases. Emerging evidence suggests that phenotypic heterogeneity of repair and inflammatory capacities of fibroblasts may contribute to the differential structural changes observed in different regions of the lung.
To investigate phenotypic differences in parenchymal and bronchial fibroblasts, either in terms of inflammation and remodelling or the ability of these fibroblasts to respond to IL-17A.
Four groups of primary fibroblasts were used: normal human bronchial fibroblast (NHBF), normal human parenchymal fibroblast (NHPF), COPD human bronchial fibroblast (CHBF) and COPD human parenchymal fibroblast (CHPF). Cytokine and extracellular matrix (ECM) expression were measured at baseline and after stimulation with IL-17A. Actinomycin D was used to measure cytokine mRNA stability.
At baseline, we observed higher protein production of IL-6 in NHPF than NHBF, but higher levels of IL-8 and GRO-α in NHBF. IL-17A induced a higher expression of GRO-α (CXCL1) and IL-6 in NHPF than in NHBF, and a higher level of IL-8 expression in NHBF. IL-17A treatment decreased the mRNA stability of IL-6 in NHBF when compared with NHPF. CHPF expressed higher protein levels of fibronectin, collagen-I and collagen-III than CHBF, NHBF and NHPF. IL-17A increased fibronectin and collagen-III protein only in NHPF and collagen-III protein production in CHBF and CHPF.
These findings provide insight into the inflammatory and remodelling processes that may be related to the phenotypic heterogeneity of fibroblasts from airway and parenchymal regions and in their response to IL-17A.
以白细胞介素-17A（IL-17A）表达增加为特征的慢性炎症，连同气道和实质重塑是慢性肺部疾病的特征。新出现的证据表明，成纤维细胞修复和炎症能力的表型异质性可能导致在肺的不同区域观察到的不同结构变化。
研究实质和支气管成纤维细胞在炎症和重塑方面的表型差异，或这些成纤维细胞对IL-17A的反应能力。
使用四组成纤维细胞原代培养物：正常人支气管成纤维细胞（NHBF）、正常人实质成纤维细胞（NHPF）、慢性阻塞性肺疾病（COPD）患者支气管成纤维细胞（CHBF）和COPD患者实质成纤维细胞（CHPF）。在基线时以及用IL-17A刺激后测量细胞因子和细胞外基质（ECM）的表达。放线菌素D用于测量细胞因子mRNA稳定性。
在基线时，我们观察到NHPF中IL-6的蛋白产生高于NHBF，但NHBF中IL-8和生长调节致癌基因-α（GRO-α）水平更高。与NHBF相比，IL-17A诱导NHPF中GRO-α（CXCL1）和IL-6的表达更高，而NHBF中IL-8表达水平更高。与NHPF相比，IL-17A处理降低了NHBF中IL-6的mRNA稳定性。CHPF中纤连蛋白、I型胶原和III型胶原的蛋白水平高于CHBF、NHBF和NHPF。IL-17A仅增加了NHPF中的纤连蛋白和III型胶原蛋白以及CHBF和CHPF中III型胶原蛋白的产生。
这些发现为可能与气道和实质区域成纤维细胞表型异质性及其对IL-17A反应相关的炎症和重塑过程提供了见解。
