Epithelial-interleukin-1 inhibits collagen formation by airway fibroblasts: Implications for asthmaOsei, E. T., B Mostaço-Guidolin, L., Hsieh, A., Warner, S. M., Al-Fouadi, M., Wang, M., Cole, D. J., Maksym, G. N., S Hallstrand, T., Timens, W., Brandsma, C-A., Heijink, I. H. & Hackett, T-L., 26-May-2020, In : Scientific Reports. 10, 1, 14 p., 8721.
Research output: Contribution to journal › Article › Academic › peer-review
In asthma, the airway epithelium has an impaired capacity to differentiate and plays a key role in the development of airway inflammation and remodeling through mediator release. The study objective was to investigate the release of (IL)-1 family members from primary airway epithelial-cells during differentiation, and how they affect primary airway fibroblast (PAF)-induced inflammation, extracellular matrix (ECM) production, and collagen I remodeling. The release of IL-1α/β and IL-33 during airway epithelial differentiation was assessed over 20-days using air-liquid interface cultures. The effect of IL-1 family cytokines on airway fibroblasts grown on collagen-coated well-plates and 3-dimensional collagen gels was assessed by measurement of inflammatory mediators and ECM proteins by ELISA and western blot, as well as collagen fiber formation using non-linear optical microscopy after 24-hours. The production of IL-1α is elevated in undifferentiated asthmatic-PAECs compared to controls. IL-1α/β induced fibroblast pro-inflammatory responses (CXCL8/IL-8, IL-6, TSLP, GM-CSF) and suppressed ECM-production (collagen, fibronectin, periostin) and the cell's ability to repair and remodel fibrillar collagen I via LOX, LOXL1 and LOXL2 activity, as confirmed by inhibition with β-aminopropionitrile. These data support a role for epithelial-derived-IL-1 in the dysregulated repair of the asthmatic-EMTU and provides new insights into the contribution of airway fibroblasts in inflammation and airway remodeling in asthma.
|Number of pages||14|
|Publication status||Published - 26-May-2020|