IL-37 Attenuates Lung Fibrosis by Inducing Autophagy and Regulating TGF-beta 1 Production in Mice
- Authors
- Kim, Mi So; Baek, Ae Rin; Lee, June Hyuk; Jang, An Soo; Kim, Do Jin; Chin, Su Sie; Park, Sung Woo
- Issue Date
- 15-Oct-2019
- Publisher
- American Association of Immunologists
- Keywords
- 호흡기내과
- Citation
- Journal of Immunology, v.203, no.8, pp 2265 - 2275
- Pages
- 11
- Journal Title
- Journal of Immunology
- Volume
- 203
- Number
- 8
- Start Page
- 2265
- End Page
- 2275
- URI
- https://scholarworks.bwise.kr/sch/handle/2021.sw.sch/4141
- DOI
- 10.4049/jimmunol.1801515
- ISSN
- 0022-1767
1550-6606
- Abstract
- Idiopathic pulmonary fibrosis (IPF) is a progressive and destructive lung disease with a poor prognosis resulting in a high mortality rate. IL-37 is an anti-inflammatory cytokine that inhibits innate and adaptive immunity by downregulating proinflammatory mediators and pathways. However, the exact role of IL-37 in lung fibrosis is unclear. In this study, we found that the IL-37 protein was expressed in alveolar epithelial cells (AECs) and alveolar macrophages in healthy controls but significantly reduced in patients with IPF. IL-37 significantly inhibited oxidative stress-induced primary mouse AEC death in a dose-dependent manner, and knockdown of IL-37 significantly potentiated human lung cancer-derived AEC (A549 cells) death. IL-37 attenuated constitutive mRNA and protein expression of fibronectin and collagen I in primary human lung fibroblasts. IL-37 inhibited TGF-beta 1-induced lung fibroblast proliferation and downregulated the TGF-beta 1 signaling pathway. Moreover, IL-37 enhanced beclin-1-dependent autophagy and autophagy modulators in IPF fibroblasts. IL-37 significantly decreased inflammation and collagen deposition in bleomycin-exposed mouse lungs, which was reversed by treatment with the autophagy inhibitor 3-methyladenine. Our findings suggested that a decrease in IL-37 may be involved in the progression of IPF and that IL-37 inhibited TGF-beta 1 signaling and enhancement of autophagy in IPF fibroblasts. Given its antifibrotic activity, IL-37 could be a therapeutic target in fibrotic lung diseases, including IPF.
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Collections - College of Medicine > Department of Pathology > 1. Journal Articles
- College of Medicine > Department of Internal Medicine > 1. Journal Articles
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