Format

Send to

Choose Destination
Respir Res. 2018 Sep 26;19(1):188. doi: 10.1186/s12931-018-0863-3.

IL-32γ attenuates airway fibrosis by modulating the integrin-FAK signaling pathway in fibroblasts.

Author information

1
Asan Institute for Life Science, Seoul, Korea.
2
Department of Internal Medicine, Division of Allergy and Clinical Immunology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 138-736, Korea.
3
Department of Internal medicine, Division of Allergy and Respiratory Medicine, Konkuk University Medical Center, Seoul, Korea.
4
Department of Internal Medicine, Jeju National University School of Medicine, Jeju, Korea.
5
Department of Convergence Medicine, University of Ulsan, Seoul, Korea.
6
Laboratory of Cytokine Immunology, Institute of Biomedical Science and Technology, College of Medicine, Konkuk University, Seoul, Korea.
7
Department of Internal Medicine, Division of Allergy and Clinical Immunology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 138-736, Korea. yscho@amc.seoul.kr.

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)-β-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-β. 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.

KEYWORDS:

Airway inflammation; Asthma; Interleukin-32γ; Pulmonary fibrosis; Subepithelial fibrosis

PMID:
30257681
PMCID:
PMC6158920
DOI:
10.1186/s12931-018-0863-3
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for BioMed Central Icon for PubMed Central
Loading ...
Support Center