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Lactobacillus paracasei-derived extracellular vesicles alleviate neutrophilic asthma by inhibiting the JNK pathway in airway epithelium

Authors
Sim, S | Park, HJ | Kim, YK | Choi, Y | Park, HS
Citation
Allergology international, 73(2). : 302-312, 2024
Journal Title
Allergology international
ISSN
1323-89301440-1592
Abstract
Background: Lactobacillus paracasei has been known to reduce airway resistance and inflammation in asthma. However, the therapeutic effect of its extracellular vesicles (EVs) in patients with asthma remains unclear. Methods: To validate the clinical relevance of L. paracasei-derived EVs (LpEV) in asthma, the composition of gut microbial EVs was verified by metagenomics in LPS-induced C57BL/6 mice. The components of proteins and metabolites in LpEV were identified by peptide mass fingerprinting and metabolomic analysis. The serum levels of specific IgG1 or IgG4 antibodies to LpEV were compared by ELISA between patients with eosinophilic asthma (EA, n = 10) and those with neutrophilic asthma (NA, n = 10) as well as with healthy controls (HCs, n = 10). Finally, therapeutic effects of LpEV and their metabolites in asthma were validated in vivo/in vitro. Results: Significantly lower proportions of EVs derived from Lactobacillus at the genus level were noted in mice with NA than in control mice. Moreover, the serum levels of LpEV-specific IgG4, but not IgG1, were lower in patients with NA than in those with EA or in HCs and positively correlated with FEV1 (%) values. In addition, oral administration of LpEV reduced airway resistance and inflammation in mice with NA. Finally, LpEV and their 3 metabolites (dodecanoic acid, palmitoleic acid, and D-(−)-tagatose) significantly inhibited JNK phosphorylation/IL-8 production in airway epithelium in vitro. Conclusions: These findings suggest that LpEV may have a therapeutic potential targeting NA by suppressing the JNK pathway and proinflammatory cytokine production in airway epithelium.
Keywords

MeSH

DOI
10.1016/j.alit.2023.10.008
PMID
37953104
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Allergy
Ajou Authors
박, 해심
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