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Ivermectin Affects Neutrophil-Induced Inflammation through Inhibition of Hydroxylysine but Stimulation of Cathepsin G and Phenylalanine Secretionстатья
Статья опубликована в высокорейтинговом журнале
Статья опубликована в журнале из списка Web of Science и/или Scopus- Авторы: Galkina Svetlana I., Golenkina Ekaterina A., Serebryakova Marina V., Fedorova Natalia V., Ksenofontov Alexander L., Stadnichuk Vladimir I., Sud’ina Galina F.
- Журнал: BIOMEDICINES
- Том: 10
- Номер: 12
- Год издания: 2022
- Первая страница: 3284
- DOI: 10.3390/biomedicines10123284
- Аннотация: The invasion and integrin-dependent adhesion of neutrophils to lung tissues and theirsecretion lead to the development of pneumonia in various pulmonary pathologies, includingacute respiratory distress syndrome in coronavirus disease. We studied the effect of ivermectin, apossible therapeutic agent for inflammation and cancer, on integrin-dependent neutrophil adhesionto fibronectin and the concomitant secretion. Ivermectin did not affect the attachment of neutrophilsto the substrate and the reactive oxygen species production but sharply inhibited the adhesioninducedrelease of hydroxylysine and stimulated the release of phenylalanine and cathepsin G.Hydroxylysine is a product of lysyl hydroxylase, which is overexpressed in tumor cells with anincreased ability to invade and metastasize. The inhibition of hydroxylysine release by ivermectin, byanalogy, may indicate the suppression of neutrophil invasion into tissue. The increase in the releaseof phenylalanine in our experiments coincided with the secretion of cathepsin G, which indicatesthe possible role of this enzyme in the cleavage of phenylalanine. What is the substrate in such areaction is unknown. We demonstrated that exogenously added angiotensin II (1–8) can serve as asubstrate for phenylalanine cleavage. Mass spectrometry revealed the formation of angiotensin II(1–7) in the secretion of neutrophils, which attached to fibronectin in the presence of ivermectin andexogenous angiotensin II (1–8), indicating a possible involvement of ivermectin in the inactivation ofangiotensin II.
- Добавил в систему: Галкина Светлана Ивановна