Interleukin-19 Aggravates Pulmonary Fibrosis via Activating Fibroblast through TGF-β/Smad Pathway
Yu Wang1, Sibo Sun1, Kai Wang1
1Jiangsu Provincial Key Laboratory of Geriatrics, Department of Geriatrics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Mediators of Inflammation
|March 14, 2022
Summary
Interleukin-19 (IL-19) promotes lung fibroblast activity and worsens lung fibrosis. Targeting IL-19 may offer a new therapeutic strategy for idiopathic pulmonary fibrosis (IPF).
Area of Science:
- Pulmonary Medicine
- Immunology
- Cell Biology
Background:
- Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease with no cure.
- Cytokines and their receptors mediate cell communication in injured lungs.
- Interleukin-19 (IL-19) has shown detrimental effects in respiratory diseases, but its role in lung fibrosis was unknown.
Purpose of the Study:
- To investigate the role of IL-19 in the pathogenesis of lung fibrosis.
- To explore the potential of IL-19 as a therapeutic target for IPF.
Main Methods:
- Bioinformatic, immunohistochemistry, and western blot analyses assessed IL-19 expression in human and mouse fibrotic lung tissues.
- Cell-based assays (CCK-8, transwell, flow cytometry) evaluated IL-19's impact on lung fibroblast behavior.
- In vivo studies using bleomycin-induced lung fibrosis in mice elucidated IL-19's profibrotic effects.
Main Results:
- IL-19 expression was significantly upregulated in fibrotic lung tissues.
- IL-19 enhanced lung fibroblast proliferation, invasion, and myofibroblast differentiation while inhibiting apoptosis.
- IL-19 exacerbated lung fibrosis in a murine model, effects partially reversed by a TGF-β/Smad inhibitor.
Conclusions:
- IL-19 plays a direct profibrotic role by acting on lung fibroblasts.
- Targeting IL-19 presents a promising therapeutic avenue for treating pulmonary fibrosis.
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