Interleukin-38 ameliorates poly(I:C) induced lung inflammation : therapeutic implications in respiratory viral infections
Interleukin-38 has recently been shown to have anti-inflammatory properties in lung inflammatory diseases. However, the effects of IL-38 in viral pneumonia remains unknown. In the present study, we demonstrate that circulating IL-38 concentrations together with IL-36α increased significantly in influenza and COVID-19 patients, and the level of IL-38 and IL-36α correlated negatively and positively with disease severity and inflammation, respectively. In the co-cultured human respiratory epithelial cells with macrophages to mimic lung microenvironment in vitro, IL-38 was able to alleviate inflammatory responses by inhibiting poly(I:C)-induced overproduction of pro-inflammatory cytokines and chemokines through intracellular STAT1, STAT3, p38 MAPK, ERK1/2, MEK, and NF-κB signaling pathways. Intriguingly, transcriptomic profiling revealed that IL-38 targeted genes were associated with the host innate immune response to virus. We also found that IL-38 counteracts the biological processes induced by IL-36α in the co-culture. Furthermore, the administration of recombinant IL-38 could mitigate poly I:C-induced lung injury, with reduced early accumulation of neutrophils and macrophages in bronchoalveolar lavage fluid, activation of lymphocytes, production of pro-inflammatory cytokines and chemokines and permeability of the alveolar-epithelial barrier. Taken together, our study indicates that IL-38 plays a crucial role in protection from exaggerated pulmonary inflammation during poly(I:C)-induced pneumonia, thereby providing the basis of a novel therapeutic target for respiratory viral infections.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:12 |
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| Enthalten in: |
Cell death & disease - 12(2021), 1 vom: 07. Jan., Seite 53 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Gao, Xun [VerfasserIn] |
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| Links: |
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| Themen: |
Cytokines |
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| Anmerkungen: |
Date Completed 22.01.2021 Date Revised 22.01.2021 published: Electronic Citation Status MEDLINE |
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| doi: |
10.1038/s41419-020-03283-2 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM319781135 |
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| 520 | |a Interleukin-38 has recently been shown to have anti-inflammatory properties in lung inflammatory diseases. However, the effects of IL-38 in viral pneumonia remains unknown. In the present study, we demonstrate that circulating IL-38 concentrations together with IL-36α increased significantly in influenza and COVID-19 patients, and the level of IL-38 and IL-36α correlated negatively and positively with disease severity and inflammation, respectively. In the co-cultured human respiratory epithelial cells with macrophages to mimic lung microenvironment in vitro, IL-38 was able to alleviate inflammatory responses by inhibiting poly(I:C)-induced overproduction of pro-inflammatory cytokines and chemokines through intracellular STAT1, STAT3, p38 MAPK, ERK1/2, MEK, and NF-κB signaling pathways. Intriguingly, transcriptomic profiling revealed that IL-38 targeted genes were associated with the host innate immune response to virus. We also found that IL-38 counteracts the biological processes induced by IL-36α in the co-culture. Furthermore, the administration of recombinant IL-38 could mitigate poly I:C-induced lung injury, with reduced early accumulation of neutrophils and macrophages in bronchoalveolar lavage fluid, activation of lymphocytes, production of pro-inflammatory cytokines and chemokines and permeability of the alveolar-epithelial barrier. Taken together, our study indicates that IL-38 plays a crucial role in protection from exaggerated pulmonary inflammation during poly(I:C)-induced pneumonia, thereby providing the basis of a novel therapeutic target for respiratory viral infections | ||
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| 700 | 1 | |a Lui, Grace Chung Yan |e verfasserin |4 aut | |
| 700 | 1 | |a Hui, David Shu Cheong |e verfasserin |4 aut | |
| 700 | 1 | |a Chu, Ida Miu-Ting |e verfasserin |4 aut | |
| 700 | 1 | |a Sun, Xiaoyu |e verfasserin |4 aut | |
| 700 | 1 | |a Tsang, Miranda Sin-Man |e verfasserin |4 aut | |
| 700 | 1 | |a Chan, Ben Chung Lap |e verfasserin |4 aut | |
| 700 | 1 | |a Lam, Christopher Wai-Kei |e verfasserin |4 aut | |
| 700 | 1 | |a Wong, Chun-Kwok |e verfasserin |4 aut | |
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