IL-25 Induced ROS-Mediated M2 Macrophage Polarization Via AMPK-Associated Mitophagy

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2022 Jan 11

PMID 35008429

Authors

Mei-Lan Tsai

Yi-Giien Tsai

Yu-Chih Lin

Ya-Ling Hsu

Yi-Ting Chen

Ming-Kai Tsai

Wei-Ting Liao

Yi-Ching Lin

Chih-Hsing Hung

Affiliations

Soon will be listed here.

Abstract

Interleukin (IL)-25 is a cytokine released by airway epithelial cells responding to pathogens. Excessive production of reactive oxygen species (ROS) leads to airway inflammation and remodeling in asthma. Mitochondria are the major source of ROS. After stress, defective mitochondria often undergo selective degradation, known as mitophagy. In this study, we examined the effects of IL-25 on ROS production and mitophagy and investigated the underlying mechanisms. The human monocyte cell line was pretreated with IL-25 at different time points. ROS production was measured by flow cytometry. The involvement of mitochondrial activity in the effects of IL-25 on ROS production and subsequent mitophagy was evaluated by enzyme-linked immunosorbent assay, Western blotting, and confocal microscopy. IL-25 stimulation alone induced ROS production and was suppressed by N-acetylcysteine, vitamin C, antimycin A, and MitoTEMPO. The activity of mitochondrial complex I and complex II/III and the levels of p-AMPK and the mitophagy-related proteins were increased by IL-25 stimulation. The CCL-22 secretion was increased by IL-25 stimulation and suppressed by mitophagy inhibitor treatment and PINK1 knockdown. The Th2-like cytokine IL-25 can induce ROS production, increase mitochondrial respiratory chain complex activity, subsequently activate AMPK, and induce mitophagy to stimulate M2 macrophage polarization in monocytes.

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References

Divekar R, Kita H . Recent advances in epithelium-derived cytokines (IL-33, IL-25, and thymic stromal lymphopoietin) and allergic inflammation. Curr Opin Allergy Clin Immunol. 2014; 15(1):98-103. PMC: 4346181. DOI: 10.1097/ACI.0000000000000133. View

Yao X, Sun Y, Wang W, Sun Y . Interleukin (IL)-25: Pleiotropic roles in asthma. Respirology. 2015; 21(4):638-47. DOI: 10.1111/resp.12707. View

Han Y, Wang Q, Song P, Zhu Y, Zou M . Redox regulation of the AMP-activated protein kinase. PLoS One. 2010; 5(11):e15420. PMC: 2974634. DOI: 10.1371/journal.pone.0015420. View

Reinmuth-Selzle K, Kampf C, Lucas K, Lang-Yona N, Frohlich-Nowoisky J, Shiraiwa M . Air Pollution and Climate Change Effects on Allergies in the Anthropocene: Abundance, Interaction, and Modification of Allergens and Adjuvants. Environ Sci Technol. 2017; 51(8):4119-4141. PMC: 5453620. DOI: 10.1021/acs.est.6b04908. View

Fort M, Cheung J, Yen D, Li J, Zurawski S, Lo S . IL-25 induces IL-4, IL-5, and IL-13 and Th2-associated pathologies in vivo. Immunity. 2002; 15(6):985-95. DOI: 10.1016/s1074-7613(01)00243-6. View

Valente E, Abou-Sleiman P, Caputo V, Muqit M, Harvey K, Gispert S . Hereditary early-onset Parkinson's disease caused by mutations in PINK1. Science. 2004; 304(5674):1158-60. DOI: 10.1126/science.1096284. View

Wood L, Wark P, Garg M . Antioxidant and anti-inflammatory effects of resveratrol in airway disease. Antioxid Redox Signal. 2010; 13(10):1535-48. DOI: 10.1089/ars.2009.3064. View

Tworek D, Smith S, Salter B, Baatjes A, Scime T, Watson R . IL-25 Receptor Expression on Airway Dendritic Cells after Allergen Challenge in Subjects with Asthma. Am J Respir Crit Care Med. 2015; 193(9):957-64. DOI: 10.1164/rccm.201509-1751OC. View

Tan H, Wang N, Li S, Hong M, Wang X, Feng Y . The Reactive Oxygen Species in Macrophage Polarization: Reflecting Its Dual Role in Progression and Treatment of Human Diseases. Oxid Med Cell Longev. 2016; 2016:2795090. PMC: 4837277. DOI: 10.1155/2016/2795090. View

10.

Sanchez-Duarte E, Cortes-Rojo C, Sanchez-Briones L, Campos-Garcia J, Saavedra-Molina A, Delgado-Enciso I . Nicorandil Affects Mitochondrial Respiratory Chain Function by Increasing Complex III Activity and ROS Production in Skeletal Muscle Mitochondria. J Membr Biol. 2020; 253(4):309-318. DOI: 10.1007/s00232-020-00129-y. View

11.

Feng J, Li L, Ou Z, Li Q, Gong B, Zhao Z . IL-25 stimulates M2 macrophage polarization and thereby promotes mitochondrial respiratory capacity and lipolysis in adipose tissues against obesity. Cell Mol Immunol. 2017; 15(5):493-505. PMC: 6068125. DOI: 10.1038/cmi.2016.71. View

12.

Kabata H, Moro K, Koyasu S, Asano K . Group 2 innate lymphoid cells and asthma. Allergol Int. 2015; 64(3):227-34. DOI: 10.1016/j.alit.2015.03.004. View

13.

Bingol B, Sheng M . Mechanisms of mitophagy: PINK1, Parkin, USP30 and beyond. Free Radic Biol Med. 2016; 100:210-222. DOI: 10.1016/j.freeradbiomed.2016.04.015. View

14.

Lin X, Qiu B, Ma M, Zhang R, Hsu S, Liu H . Suppressing DRP1-mediated mitochondrial fission and mitophagy increases mitochondrial apoptosis of hepatocellular carcinoma cells in the setting of hypoxia. Oncogenesis. 2020; 9(7):67. PMC: 7359348. DOI: 10.1038/s41389-020-00251-5. View

15.

Paradies G, Petrosillo G, Pistolese M, Di Venosa N, Federici A, Ruggiero F . Decrease in mitochondrial complex I activity in ischemic/reperfused rat heart: involvement of reactive oxygen species and cardiolipin. Circ Res. 2003; 94(1):53-9. DOI: 10.1161/01.RES.0000109416.56608.64. View

16.

Kirkham P, Rahman I . Oxidative stress in asthma and COPD: antioxidants as a therapeutic strategy. Pharmacol Ther. 2006; 111(2):476-94. DOI: 10.1016/j.pharmthera.2005.10.015. View

17.

Wang Y, Angkasekwinai P, Lu N, Voo K, Arima K, Hanabuchi S . IL-25 augments type 2 immune responses by enhancing the expansion and functions of TSLP-DC-activated Th2 memory cells. J Exp Med. 2007; 204(8):1837-47. PMC: 2118667. DOI: 10.1084/jem.20070406. View

18.

Hewitt R, Lloyd C . Regulation of immune responses by the airway epithelial cell landscape. Nat Rev Immunol. 2021; 21(6):347-362. PMC: 7804588. DOI: 10.1038/s41577-020-00477-9. View

19.

Osborn-Heaford H, Ryan A, Murthy S, Racila A, He C, Sieren J . Mitochondrial Rac1 GTPase import and electron transfer from cytochrome c are required for pulmonary fibrosis. J Biol Chem. 2011; 287(5):3301-12. PMC: 3270985. DOI: 10.1074/jbc.M111.308387. View

20.

Jornayvaz F, Shulman G . Regulation of mitochondrial biogenesis. Essays Biochem. 2010; 47:69-84. PMC: 3883043. DOI: 10.1042/bse0470069. View