Τίτλος:
Increased autotaxin levels in severe covid-19, correlating with il-6 levels, endothelial dysfunction biomarkers, and impaired functions of dendritic cells
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
Autotaxin (ATX; ENPP2) is a secreted lysophospholipase D catalyzing the extracellular production of lysophosphatidic acid (LPA), a pleiotropic signaling phospholipid. Genetic and pharmacologic studies have previously established a pathologic role for ATX and LPA signaling in pulmonary injury, inflammation, and fibrosis. Here, increased ENPP2 mRNA levels were detected in immune cells from nasopharyngeal swab samples of COVID-19 patients, and increased ATX serum levels were found in severe COVID-19 patients. ATX serum levels correlated with the corresponding increased serum levels of IL-6 and endothelial damage biomarkers, suggesting an interplay of the ATX/LPA axis with hyperinflammation and the associated vascular dysfunction in COVID-19. Accordingly, dexamethasone (Dex) treatment of mechanically ventilated patients reduced ATX levels, as shown in two independent cohorts, indicating that the therapeutic benefits of Dex include the suppression of ATX. Moreover, large scale analysis of multiple single cell RNA sequencing datasets revealed the expression landscape of ENPP2 in COVID-19 and further suggested a role for ATX in the homeostasis of dendritic cells, which exhibit both numerical and functional deficits in COVID-19. Therefore, ATX has likely a multifunctional role in COVID-19 pathogenesis, suggesting that its pharmacological targeting might represent an additional therapeutic option, both during and after hospitalization. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.
Συγγραφείς:
Nikitopoulou, I.
Fanidis, D.
Ntatsoulis, K.
Moulos, P.
Mpekoulis, G.
Evangelidou, M.
Vassiliou, A.G.
Dimakopoulou, V.
Jahaj, E.
Tsipilis, S.
Orfanos, S.E.
Dimopoulou, I.
Angelakis, E.
Akinosoglou, K.
Vassilaki, N.
Tzouvelekis, A.
Kotanidou, A.
Aidinis, V.
Περιοδικό:
International Journal of Molecular Sciences
Λέξεις-κλειδιά:
alkylglycerophosphoethanolamine phosphodiesterase; biological marker; dexamethasone; IL6 protein, human; interleukin 6; phosphodiesterase; phosphodiesterase inhibitor, adult; aged; artificial ventilation; blood; cohort analysis; dendritic cell; diagnosis; drug effect; female; human; immunology; information processing; isolation and purification; male; metabolism; middle aged; pathology; severity of illness index; signal transduction; single cell analysis; therapy; vascular endothelium; very elderly, Adult; Aged; Aged, 80 and over; Biomarkers; Cohort Studies; COVID-19; Datasets as Topic; Dendritic Cells; Dexamethasone; Endothelium, Vascular; Female; Humans; Interleukin-6; Male; Middle Aged; Phosphodiesterase Inhibitors; Phosphoric Diester Hydrolases; Respiration, Artificial; RNA-Seq; SARS-CoV-2; Severity of Illness Index; Signal Transduction; Single-Cell Analysis
DOI:
10.3390/ijms221810006
