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Syringaresinol alleviates IgG immune complex induced acute lung injury via activating PPARγ and suppressing pyroptosis.
- Source :
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International Immunopharmacology . Nov2023:Part B, Vol. 124, pN.PAG-N.PAG. 1p. - Publication Year :
- 2023
-
Abstract
- • We constructed SYG alleviates IgG-IC-induced acute lung injury via PPARγ target in vivio and vitro. • We identified SYG inhibits IgG-IC-induced pyroptosis in mice model and MH-S cells. • SYG may regulate the NLRP3/ASC/GSDMD/Caspase-1 pathway through Hdac11 by transcriptomic analysis flow analysis. Acute lung injury (ALI) is a life-threatening condition characterized by severe lung inflammation and tissue damage. In this study, we investigate the potential therapeutic efficacy of (+)-Syringaresinol (SYG), a natural compound known for its antioxidant and anti-inflammatory properties, in alleviating ALI induced by IgG immune complexes (IgG-IC). Using MH-S cells as a model, we explore SYG's ability to target peroxisome proliferator-activated receptor gamma (PPARγ) and its anti-inflammatory properties. Our comprehensive investigation aims to elucidate the specific molecular mechanisms underlying SYG's effects against pyroptosis, as revealed through transcriptomic analysis. Validation in C57BL/6 mice provides in vivo support. Our findings indicate that SYG effectively mitigates IgG-IC-induced lung damage, as evidenced by a significant reduction in lung inflammation and tissue injury. SYG treatment notably decreases pro-inflammatory cytokine levels (TNF-α, IL-6, IL-1β) in both lung tissue and cells. Molecular docking analysis reveals SYG's robust binding to PPARγ, leading to the inhibition of IgG-IC-induced inflammatory signaling pathways. Additionally, transcriptomic analysis unveils SYG's potential in suppressing macrophage pyroptosis, potentially through the downregulation of key inflammatory mediators (NLRP3, GSDMD, Caspase-1). In summary, our study presents compelling evidence supporting SYG as an effective therapeutic agent for ALI. SYG's activation of PPARγ contributes to the suppression of NF-κB and C/EBPs expression, thereby mitigating inflammation. Moreover, SYG demonstrates the ability to inhibit macrophage pyroptosis by targeting the NLRP3/GSDMD/caspase-1 axis. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 15675769
- Volume :
- 124
- Database :
- Academic Search Index
- Journal :
- International Immunopharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 173235257
- Full Text :
- https://doi.org/10.1016/j.intimp.2023.111071