IL-5 signaling in asthmatic derived fibroblasts exacerbates airway remodeling through ECM dysregulation and apoptosis resistance

BACKGROUND: Airway remodelling, a critical feature of severe asthma, involves fibroblast-driven extracellular matrix (ECM) dysregulation. While IL-5 is pivotal in eosinophilic inflammation, its direct role in fibroblast-mediated fibrosis remains undefined. METHODS: Primary lung fibroblasts from asthmatic and healthy donors were stimulated with 0.5 ng/ml of IL-5 for several time points. ECM components, Matrix metalloproteinases (MMPs), Tissue inhibitor of metalloproteinases (TIMPs), and cytokines were analysed via quantitative real time-PCR (qRT-PCR), Western blot, ELISA, and flow cytometry. RNA sequencing and absolute gene set enrichment analysis (absGSEA) identified signaling pathways. Apoptosis was assessed using Annexin V/PI staining. RESULTS: IL-5 shown to markedly increase the expression of ECM proteins, including collagen I and fibronectin, in asthmatic fibroblasts. It also upregulated MMP-2 and MMP-3 expression, alongside increased levels of TIMP-1 and TIMP-2. Moreover, IL-5 promoted the secretion of IL-6 and TGF-

• Abujabal, R.
• Alanta, T. M.
• Alhamidi, R. S.
• Altaie, A. M.
• Sahnoon, L.
• Mdkhana, B.
• Mahboub, B.
• Laumonnier, Y.
• Hamoudi, R.
• Bajbouj, K.
• Hamid, Q.