Montelukast, Leukotriene Inhibitor, Reduces LPS-Induced Acute Lung Inflammation and Human Neutrophil Activation

Autor: Nilsa Regina Damaceno-Rodrigues, Nicole Cristine Rigonato-Oliveira, Alessandro Pereira da Silva, Flavio Aimbire, BreAnne MacKenzie, Jefferson Comin Jonco Aquino-Junior, Ana Roberta Almeida-Oliveira, Ana Paula Ligeiro Oliveira, Fernanda Marciano Consolim-Colombo, Rodolfo de Paula Vieira, Alana Santos-Dias, Jaime Eduardo Davino-Chiovatto, Hugo C. Castro-Faria-Neto, Auriléia Aparecida de Brito, Manoel Carneiro Oliveira-Junior
Rok vydání: 2019
Předmět:
Cyclopropanes
Lipopolysaccharides
Vascular Endothelial Growth Factor A
ARDS
Time Factors
Neutrophils
Cell
Receptors
Leukotriene B4
Acetates
Pharmacology
Bronchoalveolar Lavage
Neutrophil Activation
Leukocyte Count
Mice
0302 clinical medicine
Lymphocytes
Lung
chemistry.chemical_classification
Respiratory Distress Syndrome
Leukotriene
NF-kappa B
General Medicine
medicine.anatomical_structure
Quinolines
Cytokines
medicine.symptom
hormones
hormone substitutes
and hormone antagonists
medicine.drug
Pulmonary and Respiratory Medicine
Inflammation
Sulfides
Capillary Permeability
03 medical and health sciences
medicine
Animals
Humans
Montelukast
business.industry
Macrophages
Chemotaxis
Pneumonia
medicine.disease
respiratory tract diseases
Mice
Inbred C57BL
Enzyme
030228 respiratory system
chemistry
Leukotriene Antagonists
business
Zdroj: Archivos de Bronconeumología. 55:573-580
ISSN: 0300-2896
DOI: 10.1016/j.arbres.2019.05.003
Popis: Some pro-inflammatory lipids derived from 1 lipooxygenase enzyme are potent neutrophil chemoattractant, a cell centrally involved in acute respiratory distress syndrome (ARDS); a syndrome lacking effective treatment. Considering the beneficial effects of the leukotriene receptor inhibitor, montelukast, on other lung diseases, whether montelukast attenuates inflammation in a mouse model of ARDS, and whether it reduces LPS stimulated activation of human neutrophils was investigated.Thirty-five C57Bl/6 mice were distributed into control (PBS)+24h, LPS+24h (10μg/mouse), control+48h, LPS+48h, and LPS 48h+Montelukast (10mg/kg). In addition, human neutrophils were incubated with LPS (1μg/mL) and treated with montelukast (10μM).Oral-tracheal administration of montelukast significantly attenuated total cells (P.05), macrophages (P.05), neutrophils (P.01), lymphocytes (P.001) and total protein levels in BAL (P.05), as well as IL-6 (P.05), CXCL1/KC (P.05), IL-17 (P.05) and TNF-α (P.05). Furthermore, montelukast reduced neutrophils (P.001), lymphocytes (P.01) and macrophages (P.01) in the lung parenchyma. In addition, montelukast restored BAL VEGF levels (P.05). LTB4 receptor expression (P.001) as well as NF-κB (P.001), a downstream target of LPS, were also reduced in lung parenchymal leukocytes. Furthermore, montelukast reduced IL-8 (P.001) production by LPS-treated human neutrophils.In conclusion, montelukast efficiently attenuated both LPS-induced lung inflammation in a mouse model of ARDS and in LPS challenged human neutrophils.
Databáze: OpenAIRE
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