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Autotaxin Has a Negative Role in Systemic Inflammation

The pathogenesis of sepsis involves complex interactions and a systemic inflammatory response leading eventually to multiorgan failure. Autotaxin (ATX, ENPP2) is a secreted glycoprotein largely responsible for the extracellular production of lysophosphatidic acid (LPA), which exerts multiple effects...

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Autores principales: Nikitopoulou, Ioanna, Katsifa, Aggeliki, Kanellopoulou, Paraskevi, Jahaj, Edison, Vassiliou, Alice G., Mastora, Zafeiria, Dimopoulou, Ioanna, Orfanos, Stylianos E., Aidinis, Vassilis, Kotanidou, Anastasia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9322786/
https://www.ncbi.nlm.nih.gov/pubmed/35887265
http://dx.doi.org/10.3390/ijms23147920
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author Nikitopoulou, Ioanna
Katsifa, Aggeliki
Kanellopoulou, Paraskevi
Jahaj, Edison
Vassiliou, Alice G.
Mastora, Zafeiria
Dimopoulou, Ioanna
Orfanos, Stylianos E.
Aidinis, Vassilis
Kotanidou, Anastasia
author_facet Nikitopoulou, Ioanna
Katsifa, Aggeliki
Kanellopoulou, Paraskevi
Jahaj, Edison
Vassiliou, Alice G.
Mastora, Zafeiria
Dimopoulou, Ioanna
Orfanos, Stylianos E.
Aidinis, Vassilis
Kotanidou, Anastasia
author_sort Nikitopoulou, Ioanna
collection PubMed
description The pathogenesis of sepsis involves complex interactions and a systemic inflammatory response leading eventually to multiorgan failure. Autotaxin (ATX, ENPP2) is a secreted glycoprotein largely responsible for the extracellular production of lysophosphatidic acid (LPA), which exerts multiple effects in almost all cell types through its at least six G-protein-coupled LPA receptors (LPARs). Here, we investigated a possible role of the ATX/LPA axis in sepsis in an animal model of endotoxemia as well as in septic patients. Mice with 50% reduced serum ATX levels showed improved survival upon lipopolysaccharide (LPS) stimulation compared to their littermate controls. Similarly, mice bearing the inducible inactivation of ATX and presenting with >70% decreased ATX levels were even more protected against LPS-induced endotoxemia; however, no significant effects were observed upon the chronic and systemic transgenic overexpression of ATX. Moreover, the genetic deletion of LPA receptors 1 and 2 did not significantly affect the severity of the modelled disease, suggesting that alternative receptors may mediate LPA effects upon sepsis. In translation, ATX levels were found to be elevated in the sera of critically ill patients with sepsis in comparison with their baseline levels upon ICU admission. Therefore, the results indicate a role for ATX in LPS-induced sepsis and suggest possible therapeutic benefits of pharmacologically targeting ATX in severe, systemic inflammatory disorders.
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spelling pubmed-93227862022-07-27 Autotaxin Has a Negative Role in Systemic Inflammation Nikitopoulou, Ioanna Katsifa, Aggeliki Kanellopoulou, Paraskevi Jahaj, Edison Vassiliou, Alice G. Mastora, Zafeiria Dimopoulou, Ioanna Orfanos, Stylianos E. Aidinis, Vassilis Kotanidou, Anastasia Int J Mol Sci Article The pathogenesis of sepsis involves complex interactions and a systemic inflammatory response leading eventually to multiorgan failure. Autotaxin (ATX, ENPP2) is a secreted glycoprotein largely responsible for the extracellular production of lysophosphatidic acid (LPA), which exerts multiple effects in almost all cell types through its at least six G-protein-coupled LPA receptors (LPARs). Here, we investigated a possible role of the ATX/LPA axis in sepsis in an animal model of endotoxemia as well as in septic patients. Mice with 50% reduced serum ATX levels showed improved survival upon lipopolysaccharide (LPS) stimulation compared to their littermate controls. Similarly, mice bearing the inducible inactivation of ATX and presenting with >70% decreased ATX levels were even more protected against LPS-induced endotoxemia; however, no significant effects were observed upon the chronic and systemic transgenic overexpression of ATX. Moreover, the genetic deletion of LPA receptors 1 and 2 did not significantly affect the severity of the modelled disease, suggesting that alternative receptors may mediate LPA effects upon sepsis. In translation, ATX levels were found to be elevated in the sera of critically ill patients with sepsis in comparison with their baseline levels upon ICU admission. Therefore, the results indicate a role for ATX in LPS-induced sepsis and suggest possible therapeutic benefits of pharmacologically targeting ATX in severe, systemic inflammatory disorders. MDPI 2022-07-18 /pmc/articles/PMC9322786/ /pubmed/35887265 http://dx.doi.org/10.3390/ijms23147920 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Nikitopoulou, Ioanna
Katsifa, Aggeliki
Kanellopoulou, Paraskevi
Jahaj, Edison
Vassiliou, Alice G.
Mastora, Zafeiria
Dimopoulou, Ioanna
Orfanos, Stylianos E.
Aidinis, Vassilis
Kotanidou, Anastasia
Autotaxin Has a Negative Role in Systemic Inflammation
title Autotaxin Has a Negative Role in Systemic Inflammation
title_full Autotaxin Has a Negative Role in Systemic Inflammation
title_fullStr Autotaxin Has a Negative Role in Systemic Inflammation
title_full_unstemmed Autotaxin Has a Negative Role in Systemic Inflammation
title_short Autotaxin Has a Negative Role in Systemic Inflammation
title_sort autotaxin has a negative role in systemic inflammation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9322786/
https://www.ncbi.nlm.nih.gov/pubmed/35887265
http://dx.doi.org/10.3390/ijms23147920
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