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Blocking SphK1/S1P/S1PR1 Signaling Pathway Alleviates Lung Injury Caused by Sepsis in Acute Ethanol Intoxication Mice

Inflammation, 2021-12, Vol.44 (6), p.2170-2179 [Peer Reviewed Journal]

The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2021 ;2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature. ;The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2021. ;ISSN: 0360-3997 ;EISSN: 1573-2576 ;DOI: 10.1007/s10753-021-01490-3 ;PMID: 34109517

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Title:
Blocking SphK1/S1P/S1PR1 Signaling Pathway Alleviates Lung Injury Caused by Sepsis in Acute Ethanol Intoxication Mice
Author: Chen, Liang ; Li, Lingling ; Song, Yong ; Lv, Tangfeng
Subjects: Alcoholic Intoxication - complications ; Animals ; Apoptosis ; Apoptosis - drug effects ; Biomedical and Life Sciences ; Biomedicine ; Bronchus ; Cecum ; Cytokines - metabolism ; Disease Models, Animal ; Edema ; Enzyme Inhibitors - pharmacology ; Enzyme-linked immunosorbent assay ; Ethanol ; IL-1β ; Immunology ; Inflammation ; Inflammation Mediators - metabolism ; Interleukin 18 ; Internal Medicine ; Intoxication ; Kinases ; Leukocytes (neutrophilic) ; Lung - drug effects ; Lung - enzymology ; Lung - pathology ; Lung Injury - enzymology ; Lung Injury - etiology ; Lung Injury - pathology ; Lung Injury - prevention & control ; Lungs ; Lysophospholipids - metabolism ; Male ; Metastases ; Methanol - pharmacology ; Mice ; Mice, Inbred C57BL ; Neutrophil Infiltration - drug effects ; Nitric oxide ; Original ; Original Article ; Oxidative Stress - drug effects ; Pathology ; Permeability ; Peroxidase ; Pharmacology/Toxicology ; Phosphotransferases (Alcohol Group Acceptor) - antagonists & inhibitors ; Phosphotransferases (Alcohol Group Acceptor) - metabolism ; Pneumonia - enzymology ; Pneumonia - etiology ; Pneumonia - pathology ; Pneumonia - prevention & control ; Pulmonary Edema - enzymology ; Pulmonary Edema - etiology ; Pulmonary Edema - pathology ; Pulmonary Edema - prevention & control ; Pyrrolidines - pharmacology ; Rheumatology ; Sepsis ; Sepsis - complications ; Sepsis - drug therapy ; Sepsis - enzymology ; Signal Transduction ; Sphingosine - analogs & derivatives ; Sphingosine - metabolism ; Sphingosine 1-phosphate ; Sphingosine kinase ; Sphingosine-1-Phosphate Receptors - metabolism ; Sulfones - pharmacology ; Tumor necrosis factor-TNF ; Tumor necrosis factor-α
Is Part Of: Inflammation, 2021-12, Vol.44 (6), p.2170-2179
Description: Acute ethanol intoxication increases the risk of sepsis and aggravates the symptoms of sepsis and lung injury. Therefore, this study aimed to explore whether sphingosine kinase 1 (SphK1)/sphingosine-1-phosphate (S1P)/S1P receptor 1 (S1PR1) signaling pathway functions in lung injury caused by acute ethanol intoxication-enhanced sepsis, as well as its underlying mechanism. The acute ethanol intoxication model was simulated by intraperitoneally administering mice with 32% ethanol solution, and cecal ligation and puncture (CLP) was used to construct the sepsis model. The lung tissue damage was observed by hematoxylin-eosin (H&E) staining, and the wet-to-dry (W/D) ratio was used to evaluate the degree of pulmonary edema. Inflammatory cell counting and protein concentration in bronchoalveolar lavage fluid (BALF) were, respectively, detected by hemocytometer and bicinchoninic acid (BCA) method. The levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-1β, and IL-18 in BALF were detected by their commercial enzyme-linked immunosorbent assay (ELISA) kits. The myeloperoxidase (MPO) activity and expression of apoptosis-related proteins and SphK1/S1P/S1PR1 pathway-related proteins were, respectively, analyzed by MPO ELISA kit and Western blot analysis. The cell apoptosis in lung tissues was observed by TUNEL assay. Acute ethanol intoxication (EtOH) decreased the survival rate of mice and exacerbated the lung injury caused by sepsis through increasing pulmonary vascular permeability, neutrophil infiltration, release of inflammatory factors, and cell apoptosis. In addition, EtOH could activate the SphK1/S1P/S1PR1 pathway in CLP mice. However, PF-543, as a specific inhibitor of SphK1, could partially reverse the deleterious effects on lung injury of CLP mice. PF-543 alleviated lung injury caused by sepsis in acute ethanol intoxication rats by suppressing the SphK1/S1P/S1PR1 signaling pathway.
Publisher: New York: Springer US
Language: English
Identifier: ISSN: 0360-3997
EISSN: 1573-2576
DOI: 10.1007/s10753-021-01490-3
PMID: 34109517
Source: AUTh Library subscriptions: ProQuest Central
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Blocking SphK1/S1P/S1PR1 Signaling Pathway Alleviates Lung Injury Caused by Sepsis in Acute Ethanol Intoxication Mice

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