Interleukin-38 Overexpression Prevents Bleomycin-induced Mouse Pulmonary Fibrosis

Overview

Journal Naunyn Schmiedebergs Arch Pharmacol

Specialty Pharmacology

Date 2020 Jun 25

PMID 32577797

Citations 12

Authors

Zhiwei Xu

Xianli Yuan

Qiaoyan Gao

Yan Li

Mingcai Li

Affiliations

Soon will be listed here.

Abstract

Pulmonary fibrosis is a kind of pulmonary disorder with chronic inflammation and excessive collagen deposition, and its etiology is not clear. Interleukin (IL)-38 is a new member of IL-1 family cytokines, but its role in pulmonary fibrosis has not been elucidated. In this study, a lentivirus expressing IL-38 was injected into the nasal cavity of mice with bleomycin-induced pulmonary fibrosis. We found that IL-38 overexpression reduced the body weight loss and improved the survival of mice induced by bleomycin. Furthermore, IL-38 expression attenuated the pulmonary inflammation and fibrosis damage induced by bleomycin, decreased the production of pro-inflammatory and pro-fibrotic cytokines such as IL-1β, IL-6, IL-17A, monocyte chemoattractant protein-1, and tumor necrosis factor-α, but increased the release of anti-inflammatory cytokine IL-1 receptor antagonist (IL-1Ra) in the lungs of bleomycin-challenged mice. Our data suggest that IL-38 may inhibit bleomycin-induced pulmonary inflammation and fibrosis through its anti-inflammatory effect and regulation of IL-1β/IL-1Ra balance, and IL-38 may be a new strategy for the treatment of pulmonary fibrosis.

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References

Adamson I . Pulmonary toxicity of bleomycin. Environ Health Perspect. 1976; 16:119-26. PMC: 1475236. DOI: 10.1289/ehp.7616119. View

Ashcroft T, Simpson J, Timbrell V . Simple method of estimating severity of pulmonary fibrosis on a numerical scale. J Clin Pathol. 1988; 41(4):467-70. PMC: 1141479. DOI: 10.1136/jcp.41.4.467. View

Atamas S, White B . Cytokine regulation of pulmonary fibrosis in scleroderma. Cytokine Growth Factor Rev. 2003; 14(6):537-50. DOI: 10.1016/s1359-6101(03)00060-1. View

Barlo N, van Moorsel C, Korthagen N, Heron M, Rijkers G, Ruven H . Genetic variability in the IL1RN gene and the balance between interleukin (IL)-1 receptor agonist and IL-1β in idiopathic pulmonary fibrosis. Clin Exp Immunol. 2011; 166(3):346-51. PMC: 3232382. DOI: 10.1111/j.1365-2249.2011.04468.x. View

Beyaert R, Cuenda A, Vanden Berghe W, Plaisance S, Lee J, Haegeman G . The p38/RK mitogen-activated protein kinase pathway regulates interleukin-6 synthesis response to tumor necrosis factor. EMBO J. 1996; 15(8):1914-23. PMC: 450110. View

Boutet M, Najm A, Bart G, Brion R, Touchais S, Trichet V . IL-38 overexpression induces anti-inflammatory effects in mice arthritis models and in human macrophages in vitro. Ann Rheum Dis. 2017; 76(7):1304-1312. DOI: 10.1136/annrheumdis-2016-210630. View

Car B, Meloni F, Luisetti M, Semenzato G, GIALDRONI-GRASSI G, Walz A . Elevated IL-8 and MCP-1 in the bronchoalveolar lavage fluid of patients with idiopathic pulmonary fibrosis and pulmonary sarcoidosis. Am J Respir Crit Care Med. 1994; 149(3 Pt 1):655-9. DOI: 10.1164/ajrccm.149.3.8118632. View

Chen Y, Li C, Weng D, Song L, Tang W, Dai W . Neutralization of interleukin-17A delays progression of silica-induced lung inflammation and fibrosis in C57BL/6 mice. Toxicol Appl Pharmacol. 2013; 275(1):62-72. DOI: 10.1016/j.taap.2013.11.012. View

Chu M, Shan Tam L, Zhu J, Jiao D, Liu D, Cai Z . In vivo anti-inflammatory activities of novel cytokine IL-38 in Murphy Roths Large (MRL)/lpr mice. Immunobiology. 2016; 222(3):483-493. DOI: 10.1016/j.imbio.2016.10.012. View

10.

Claussen C, Long E . Nucleic Acid recognition by metal complexes of bleomycin. Chem Rev. 2001; 99(9):2797-816. DOI: 10.1021/cr980449z. View

11.

Dinarello C, van der Meer J . Treating inflammation by blocking interleukin-1 in humans. Semin Immunol. 2013; 25(6):469-84. PMC: 3953875. DOI: 10.1016/j.smim.2013.10.008. View

12.

Gao Q, Li Y, Pan X, Yuan X, Peng X, Li M . Lentivirus expressing soluble ST2 alleviates bleomycin-induced pulmonary fibrosis in mice. Int Immunopharmacol. 2015; 30:188-193. DOI: 10.1016/j.intimp.2015.11.015. View

13.

Garraud T, Harel M, Boutet M, Le Goff B, Blanchard F . The enigmatic role of IL-38 in inflammatory diseases. Cytokine Growth Factor Rev. 2018; 39:26-35. DOI: 10.1016/j.cytogfr.2018.01.001. View

14.

Gasse P, Mary C, Guenon I, Noulin N, Charron S, Schnyder-Candrian S . IL-1R1/MyD88 signaling and the inflammasome are essential in pulmonary inflammation and fibrosis in mice. J Clin Invest. 2007; 117(12):3786-99. PMC: 2066195. DOI: 10.1172/JCI32285. View

15.

Ge Y, Huang M, Wu Y, Dong N, Yao Y . Interleukin-38 protects against sepsis by augmenting immunosuppressive activity of CD4 CD25 regulatory T cells. J Cell Mol Med. 2019; 24(2):2027-2039. PMC: 6991686. DOI: 10.1111/jcmm.14902. View

16.

Gross T, Hunninghake G . Idiopathic pulmonary fibrosis. N Engl J Med. 2001; 345(7):517-25. DOI: 10.1056/NEJMra003200. View

17.

Huang C, Li Y, Fan X, Ma Y, Zhang M, Wang W . [IL-17A promotes pulmonary inflammation in rats with pulmonary fibrosis induced by bleomycin]. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 2014; 30(4):366-70. View

18.

Izumo T, Kondo M, Nagai A . Effects of a leukotriene B4 receptor antagonist on bleomycin-induced pulmonary fibrosis. Eur Respir J. 2009; 34(6):1444-51. DOI: 10.1183/09031936.00143708. View

19.

Kolb M, Margetts P, Anthony D, Pitossi F, Gauldie J . Transient expression of IL-1beta induces acute lung injury and chronic repair leading to pulmonary fibrosis. J Clin Invest. 2001; 107(12):1529-36. PMC: 200196. DOI: 10.1172/JCI12568. View

20.

Li Y, Gao Q, Xu K, Peng X, Yuan X, Jiang W . Interleukin-37 Attenuates Bleomycin-Induced Pulmonary Inflammation and Fibrosis in Mice. Inflammation. 2018; 41(5):1772-1779. DOI: 10.1007/s10753-018-0820-9. View