Abstract
Purpose: The purpose of the present study was to estimate the effect of shionone (SHI) on sepsis-induced acute lung injury (ALI). Methods: The cecal ligation and puncture (CLP) surgery was performed to induce sepsis in mice. Pulmonary hematoxylin and eosin staining, the wet/dry ratio, myeloperoxidase (MPO) activity, and the survival rate were detected. The RAW264.7 cells were treated with SHI and stimulated with lipopolysaccharide (LPS). The cells were also overexpressed by extracellular mechanism protein 1 (ECM1) adenovirus. The relative levels of granulocyte–macrophage colony-stimulating factor, IL-6, IL-1β, TNF-α, IL-10, and TGF-β in the serum and supernatant were measured by ELISA. The protein expressions of ECM1, p-STAT5, signal transducer and activator of transcription 5 (STAT5), p-NF-κB, nuclear factor kappa-B (NF-κB), Arg1, CD206, CD16/32, and iNOS in the CLP-induced lung tissues and LPS-induced cells were detected by western blot. The cell counts of Ly6G, F4/80, CD16/32, and CD206 were evaluated by flow cytometry. The ECM1 expression was also observed by immunohistochemistry and immunofluorescence staining. Results: As a result, the histopathological change, pulmonary edema, and the MPO activity were relieved by SHI. SHI treatment increased the percentage of neutrophil and macrophage in the bronchoalveolar lavage fluid. Besides, SHI administration inhibited pro-inflammatory cytokines and M1 phenotype indices, as well as augmented the anti-inflammatory cytokines and M2 phenotype indices. SHI also attenuated the ECM1/STAT5/NF-κB pathway both in vivo and in vitro. The overexpression of ECM1 confirmed that the regulated effect of SHI was due to ECM1 signaling. Conclusion: In conclusion, the present study suggests that SHI ameliorated sepsis-induced ALI by screwing M1 phenotype to M2 phenotype macrophage via the ECM1/STAT5/NF-κB pathway.
Highlights
Sepsis is a severe disorder featured by overwhelming systemic inflammatory reaction and causes various organ failures which are even lethal
In conclusion, the present study suggests that SHI ameliorated sepsisinduced acute lung injury (ALI) by screwing M1 phenotype to M2 phenotype macrophage via the extracellular mechanism protein 1 (ECM1)/ signal transducer and activator of transcription 5 (STAT5)/NF-κB pathway
While SHI and DXM treatments were capable of reducing these indices (p < 0.01) (Figures 1F,G), the Cecal ligation and puncture (CLP) stimulation dramatically increased serum levels of tumor necrosis factor-α (TNF-α), IL-6, and IL-1β (p < 0.01), which were decreased in the SHI and DXM groups (p < 0.01) (Figures 1H–J)
Summary
Sepsis is a severe disorder featured by overwhelming systemic inflammatory reaction and causes various organ failures which are even lethal. The cecum ligated area and puncture number are responsible for the intensity of sepsis (Zhang et al, 2021a). LPS, the outer membrane component of gram-negative bacteria, is the famous endotoxin to induce overproduction of proinflammatory cytokines (Chen et al, 2020). As one of the major complication of sepsis, acute lung injury (ALI) is the devastating disease characterized by respiratory failure, alveolar–capillary membrane barrier, pulmonary edema, and immune/inflammatory reaction. The activation of neutrophil and macrophage is the pathological hallmark of the immune/inflammatory response in ALI (Fowler et al, 2019; Zhang et al, 2021a). Most clinical therapeutic methods are conducted to prevent the symptom of sepsis-induced ALI, whereas its specific drugs are warranted
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