Journal
INTERNATIONAL IMMUNOPHARMACOLOGY
Volume 88, Issue -, Pages -Publisher
ELSEVIER
DOI: 10.1016/j.intimp.2020.106849
Keywords
Acute lung injury; Cyclic helix B peptide; NLRP3; Caspase-1; NF-kappa B
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Funding
- Research Fund of Shanghai Municipal Health Commission [2019ZB0105]
- Research Funds of Zhongshan Hospital [2019ZSYXQN34, 2019ZSQN13, 2018ZSQN53, XYYX201922]
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Acute lung injury (ALI) exhibits high clinical morbidity and mortality rates. Our previous study has indicated that the novel proteolysis-resistant cyclic helix B peptide (CHBP) exerts an anti-inflammatory effect in mice with AKI. In the present study, we evaluated the effect of CHBP in an in vivo sepsis-induced ALI model and in vitro using lipopolysaccharide (LPS) and ATP stimulated bone marrow-derived macrophages (BMDMs). For in vivo experiments, mice were randomly divided into three groups: 1) sham; 2) LPS; and 3) LPS + CHBP (n = 6). All relevant data were collected after 18 h. Following CHBP treatment, the lung function of the mice was significantly improved compared to the LPS group. CHBP administration inhibited interleukin (IL)-1 beta, IL-6, and tumor necrosis factor (TNF)-alpha production at both the protein and mRNA levels. Additionally, following CHBP treatment, the population of pulmonary macrophages decreased. Simultaneously, the proportion of caspase-1-activated alveolar macrophages was also decreased after CHBP treatment. The protein levels of NLRP3 and cleaved caspase-1 were attenuated in the lung tissue following CHBP treatment. In in vitro experiments, CHBP treatment decreased NLRP3 inflammasome expression and downstream IL-1 beta secretion, consistent with the in vivo results. In addition, CHBP reversed nuclear factor (NF)-kappa B and I-kappa B phosphorylation with a significant dose-dependent effect. Therefore, these findings suggest the potential of CHBP as a therapeutic agent in sepsis-induced ALI owing to inhibition of the NLRP3 inflammasome via the NF-kappa B pathway in macrophages.
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