Epithelial-interleukin-1 inhibits collagen formation by airway fibroblasts: Implications for asthma

Osei, 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.

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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.

Original languageEnglish
Article number8721
Number of pages14
JournalScientific Reports
Issue number1
Publication statusPublished - 26-May-2020

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