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Journal of Immunology, 2019. 203(8), 2265-2275, DOI: https://doi.org/10.4049/jimmunol.1801515
IL-37 Attenuates Lung Fibrosis by Inducing Autophagy and Regulating TGF-β1 Production in Mice
Mi So Kim, Ae Rin Baek;June Hyuk Lee;An Soo Jang;Do Jin Kim;Su Sie Chin;Sung Woo Park
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-β1 induced lung fibroblast proliferation and downregulated the TGF-β1 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-β1 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
- DOI: https://doi.org/10.4049/jimmunol.1801515
- ISBN or ISSN: 0022-1767
- 본 연구는 질병관리본부 연구개발과제연구비를 지원받아 수행되었습니다.
- This research was supported by a fund by Research of Korea Centers for Disease Control and Prevention.