IL-32γ attenuates airway fibrosis by modulating the integrin-FAK signaling pathway in fibroblasts.
Respir Res
; 19(1): 188, 2018 Sep 26.
Article
en En
| MEDLINE
| ID: mdl-30257681
ABSTRACT
BACKGROUND:
Fibrosis in severe asthma often leads to irreversible organ dysfunction. However, the mechanism that regulates fibrosis remains poorly understood. Interleukin (IL)-32 plays a role in several chronic inflammatory diseases, including severe asthma. In this study, we investigated whether IL-32 is involved in fibrosis progression in the lungs.METHODS:
Murine models of chronic airway inflammation induced by ovalbumin and Aspergillus melleus protease and bleomycin-induced pulmonary fibrosis were employed. We evaluated the degree of tissue fibrosis after treatment with recombinant IL-32γ (rIL-32γ). Expression of fibronectin and α-smooth muscle actin (α-SMA) was examined and the transforming growth factor (TGF)-ß-related signaling pathways was evaluated in activated human lung fibroblasts (MRC-5 cells) treated with rIL-32γ.RESULTS:
rIL-32γ significantly attenuated collagen deposition and α-SMA production in both mouse models. rIL-32γ inhibited the production of fibronectin and α-SMA in MRC-5 cells stimulated with TGF-ß. Additionally, rIL-32γ suppressed activation of the integrin-FAK-paxillin signaling axis but had no effect on the Smad and non-Smad signaling pathways. rIL-32γ localized outside of MRC-5 cells and inhibited the interaction between integrins and the extracellular matrix without directly binding to intracellular FAK and paxillin.CONCLUSIONS:
These results demonstrate that IL-32γ has anti-fibrotic effects and is a novel target for preventing fibrosis.Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Fibrosis Pulmonar
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Transducción de Señal
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Integrinas
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Interleucinas
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Quinasa 1 de Adhesión Focal
Tipo de estudio:
Prognostic_studies
Límite:
Animals
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Humans
Idioma:
En
Año:
2018
Tipo del documento:
Article