The activation of IL-17 signaling pathway promotes pyroptosis in pneumonia-induced sepsis.
M1/M2 polarization
Pyroptosis
T cells subsets
inflammation
pneumonia-induced sepsis
Journal
Annals of translational medicine
ISSN: 2305-5839
Titre abrégé: Ann Transl Med
Pays: China
ID NLM: 101617978
Informations de publication
Date de publication:
Jun 2020
Jun 2020
Historique:
entrez:
4
7
2020
pubmed:
4
7
2020
medline:
4
7
2020
Statut:
ppublish
Résumé
Pyroptosis is closely relevant to sepsis. However, the molecular mechanisms of pyroptosis in pneumonia-induced sepsis are still not fully understood. Thus, this study aimed to find the specific molecular pathways associated with pyroptosis and explore their relationship in pneumonia-induced sepsis. First, significant signaling pathways related to pneumonia-induced sepsis were screened by bioinformatics analysis based on GSE48080. The peripheral blood samples from patients with pneumonia-induced sepsis and healthy subjects were collected. Pneumonia-induced sepsis rat models were also established. Then, inflammatory response, pyroptosis, and regulatory T cells (Tregs)/T-helper 17 (Th17), Th1/Th2, and M1/M2 cell ratios in pneumonia-induced sepsis were evaluated. IL-17 signaling pathway was significantly related to pneumonia-induced sepsis by bioinformatics analysis. Compared with healthy groups, the higher of Th17/Treg, Th1/Th2 and M1/M2 cell radios in the patients and sepsis rat model indicated that pneumonia-induced sepsis caused a severe inflammatory response. This result was confirmed by higher levels of pro-inflammatory factors (IL-6, TNF-α, IL-1β, and IL-18) and an inflammation indicator (LDH), as well as pyroptosis occurrence in sepsis. Additionally, the up-regulation of key molecules (HMGB1, RAGE, IL-17A, TRAF6 and NK-κB) in the IL-17 signaling pathway suggested the IL-17 pathway was activated. Moreover, the release of IL-1β and IL-18 and the levels of the molecules (NLRP3, NLRC4, Cleaved caspase-1, and Cleaved GSDMD) associated with caspase-1-dependent pyroptosis were up-regulated in pneumonia-induced sepsis. As NK-κB activation can promote the development of caspase-1-dependent pyroptosis, these findings suggested that the activation of the IL-17 signaling pathway could promote pyroptosis in pneumonia-induced sepsis.
Sections du résumé
BACKGROUND
BACKGROUND
Pyroptosis is closely relevant to sepsis. However, the molecular mechanisms of pyroptosis in pneumonia-induced sepsis are still not fully understood. Thus, this study aimed to find the specific molecular pathways associated with pyroptosis and explore their relationship in pneumonia-induced sepsis.
METHODS
METHODS
First, significant signaling pathways related to pneumonia-induced sepsis were screened by bioinformatics analysis based on GSE48080. The peripheral blood samples from patients with pneumonia-induced sepsis and healthy subjects were collected. Pneumonia-induced sepsis rat models were also established. Then, inflammatory response, pyroptosis, and regulatory T cells (Tregs)/T-helper 17 (Th17), Th1/Th2, and M1/M2 cell ratios in pneumonia-induced sepsis were evaluated.
RESULTS
RESULTS
IL-17 signaling pathway was significantly related to pneumonia-induced sepsis by bioinformatics analysis. Compared with healthy groups, the higher of Th17/Treg, Th1/Th2 and M1/M2 cell radios in the patients and sepsis rat model indicated that pneumonia-induced sepsis caused a severe inflammatory response. This result was confirmed by higher levels of pro-inflammatory factors (IL-6, TNF-α, IL-1β, and IL-18) and an inflammation indicator (LDH), as well as pyroptosis occurrence in sepsis. Additionally, the up-regulation of key molecules (HMGB1, RAGE, IL-17A, TRAF6 and NK-κB) in the IL-17 signaling pathway suggested the IL-17 pathway was activated. Moreover, the release of IL-1β and IL-18 and the levels of the molecules (NLRP3, NLRC4, Cleaved caspase-1, and Cleaved GSDMD) associated with caspase-1-dependent pyroptosis were up-regulated in pneumonia-induced sepsis.
CONCLUSIONS
CONCLUSIONS
As NK-κB activation can promote the development of caspase-1-dependent pyroptosis, these findings suggested that the activation of the IL-17 signaling pathway could promote pyroptosis in pneumonia-induced sepsis.
Identifiants
pubmed: 32617294
doi: 10.21037/atm-19-1739
pii: atm-08-11-674
pmc: PMC7327349
doi:
Types de publication
Journal Article
Langues
eng
Pagination
674Informations de copyright
2020 Annals of Translational Medicine. All rights reserved.
Déclaration de conflit d'intérêts
Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/atm-19-1739). The authors have no conflicts of interest to declare.
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