Abstract
Background: Chronic obstructive pulmonary disease (COPD) is described with its clear association with cigarette smoke and other environmental aspects, but the biological elements of COPD are not fully understood. Animal models have implicated interleukin 13 (IL-13) as a critical cytokine in the development of COPD through Th type 2 immune response. To clarify the molecular determinants in the pathogenesis of COPD we performed global gene expression analysis on IL-13 treated primary cultured airway epithelium.
Materials and methods: Primary culture airway epithelial cells were subject to air liquid phase interphase (ALI), and total RNA was harvested following 30ng/mL IL-13 stimulation. mRNA was labeled and hybridized on Agilent 8x60k gene expression chips. Statistical analysis of the data were performed by R, Bioconductor and Genomica.
Results: 253 genes distinguished primary bronchial epithelial cells treated with IL-13 from the cells without treatment, given the criteria of p value<0.05 and fold change>2. Enrichment analysis suggested over expression of genes involved in response to wounding, regulation of apoptosis, extracellular matrix and plasma membrane. Aside from IL-13 receptor signaling, arachidonic acid metabolism and cytokine-cytokine receptor signals were among the up-regulated pathways in IL-13 treated cells.
Conclusions: Our experimental model reveals genes involved in epithelial membrane remodeling and arachidonic acid cascade as possible regulators in the pathogenesis of COPD through Th2 immune response. These molecular mechanisms may be prioritized as therapeutic targets in the affected patients.
- Copyright ©ERS 2015
