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- Title
Proteomic analysis and identification reveal the anti-inflammatory mechanism of clofazimine on lipopolysaccharide-induced acute lung injury in mice.
- Authors
Yang, Bo; Gao, Zhan; Li, Qi-Shuang; Zhang, Xiang-Ye; Song, Lan; Wang, Yi-Ni; Wang, Xin-Yue; Ji, Lin-Lin; Xu, Hong-Liang; Xie, Hui; Feng, Fu-Kai; Li, Xiao-Ping; Li, Wei; Wang, Rong; Wang, Guang-Shun
- 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.
- Subjects
LUNG injuries; ADULT respiratory distress syndrome; PROTEOMICS; IMMUNOLOGIC diseases; COVID-19
- Publication
Inflammation Research, 2022, Vol 71, Issue 10/11, p1327
- ISSN
1023-3830
- Publication type
Article
- DOI
10.1007/s00011-022-01623-w