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13.08.2022 | Original Paper

Proteomic analysis and identification reveal the anti-inflammatory mechanism of clofazimine on lipopolysaccharide-induced acute lung injury in mice

verfasst von: Bo Yang, Zhan Gao, Qi-Shuang Li, Xiang-Ye Zhang, Lan Song, Yi-Ni Wang, Xin-Yue Wang, Lin-Lin Ji, Hong-Liang Xu, Hui Xie, Fu-Kai Feng, Xiao-Ping Li, Wei Li, Rong Wang, Guang-Shun Wang

Erschienen in: Inflammation Research | Ausgabe 10-11/2022

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Abstract

Background and objective

Acute lung injury (ALI)/ acute respiratory distress syndrome (ARDS) was increasingly recognized as one of the most severe acute hyperimmune response of coronavirus disease 2019 (COVID-19). Clofazimine (CFZ) has attracted attention due to its anti-inflammatory property in immune diseases as well as infectious diseases. However, the role and potential molecular mechanism of CFZ in anti-inflammatory responses remain unclear.

Methods

We analyze the protein expression profiles of CFZ and LPS from Raw264.7 macrophages using quantitative proteomics. Next, the protective effect of CFZ on LPS-induced inflammatory model is assessed, and its underlying mechanism is validated by molecular biology analysis.

Results

LC–MS/MS-based shotgun proteomics analysis identified 4746 (LPS) and 4766 (CFZ) proteins with quantitative information. The key proteins and their critical signal transduction pathways including TLR4/NF-κB/HIF-1α signaling was highlighted, which was involved in multiple inflammatory processes. A further analysis of molecular biology revealed that CFZ could significantly inhibit the proliferation of Raw264.7 macrophages, decrease the levels of TNF-α and IL-1β, alleviate lung histological changes and pulmonary edema, improve the survival rate, and down-regulate TLR4/NF-κB/HIF-1α signaling in LPS model.

Conclusion

This study can provide significant insight into the proteomics-guided pharmacological mechanism study of CFZ and suggest potential therapeutic strategies for infectious disease.

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Titel: Proteomic analysis and identification reveal the anti-inflammatory mechanism of clofazimine on lipopolysaccharide-induced acute lung injury in mice
verfasst von: Bo Yang
Zhan Gao
Qi-Shuang Li
Xiang-Ye Zhang
Lan Song
Yi-Ni Wang
Xin-Yue Wang
Lin-Lin Ji
Hong-Liang Xu
Hui Xie
Fu-Kai Feng
Xiao-Ping Li
Wei Li
Rong Wang
Guang-Shun Wang
Publikationsdatum: 13.08.2022
Verlag: Springer International Publishing
Erschienen in: Inflammation Research / Ausgabe 10-11/2022
Print ISSN: 1023-3830
Elektronische ISSN: 1420-908X
DOI: https://doi.org/10.1007/s00011-022-01623-w

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Background and objective

Methods

Results

Conclusion

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