CD73-dependent adenosine dampens interleukin-1β-induced CXCL8 production in gingival fibroblasts: Association with heme oxygenase-1 and adenosine monophosphate-activated protein kinase.
5′-nucleotidase
adenosine
adenosine triphosphate
fibroblasts
gingiva
interleukin-1 beta
Journal
Journal of periodontology
ISSN: 1943-3670
Titre abrégé: J Periodontol
Pays: United States
ID NLM: 8000345
Informations de publication
Date de publication:
02 2020
02 2020
Historique:
received:
03
03
2019
revised:
30
04
2019
accepted:
20
05
2019
pubmed:
28
7
2019
medline:
3
7
2020
entrez:
27
7
2019
Statut:
ppublish
Résumé
During inflammation, stressed or infected cells can release adenosine triphosphate (ATP) to the extracellular medium, which can be hydrolyzed to adenosine by ectonucleotidases such as ectonucleoside triphosphate diphosphohydrolase 1 (CD39) and 5'-nucleotidase (CD73). The role of CD73 in the modulation of cytokine release by human gingival fibroblasts (HGFs) remains underexplored. Here, we investigated whether CD73-mediated hydrolysis of extracellular ATP (eATP) could affect interleukin (IL)-1β-induced CXCL8 secretion. The levels of mRNA expression of adenosine receptors, CD39 and CD73 of periodontitis samples were retrieved from a public database. Moreover, HGF mRNA levels were measured by quantitative reverse transcription-polymerase chain reaction (RT-qPCR) after 3, 6, or 24 hours of IL-1β stimulation. IL-1β-induced CXCL8 protein levels were measured after pretreatment with 100-µM eATP in the presence or absence of CD73 inhibitor. The effect of eATP degradation to adenosine on CXCL8 levels was investigated using agonist and antagonist of adenosine receptors. Levels of CD39, CD73, and adenosine receptor mRNA were differentially modulated by IL-1β. ATP pretreatment impaired IL-1β-induced CXCL8 secretion and required activation of heme oxygenase-1 (HO-1) and phosphorylated adenosine monophosphate-activated protein kinase (pAMPK). The inhibition of CD73 or the inhibition of adenosine receptors abrogated the ATP effect on CXCL8 secretion. CD73-generated adenosine dampens IL-1β-induced CXCL8 in HGFs and involves HO-1 and pAMPK signaling. These results imply that CD73 is a negative regulator of the inflammatory microenvironment, suggesting that this ectoenzyme could be involved in the generation of deficient CXCL8 gradient in chronic inflammation.
Sections du résumé
BACKGROUND
During inflammation, stressed or infected cells can release adenosine triphosphate (ATP) to the extracellular medium, which can be hydrolyzed to adenosine by ectonucleotidases such as ectonucleoside triphosphate diphosphohydrolase 1 (CD39) and 5'-nucleotidase (CD73). The role of CD73 in the modulation of cytokine release by human gingival fibroblasts (HGFs) remains underexplored. Here, we investigated whether CD73-mediated hydrolysis of extracellular ATP (eATP) could affect interleukin (IL)-1β-induced CXCL8 secretion.
METHODS
The levels of mRNA expression of adenosine receptors, CD39 and CD73 of periodontitis samples were retrieved from a public database. Moreover, HGF mRNA levels were measured by quantitative reverse transcription-polymerase chain reaction (RT-qPCR) after 3, 6, or 24 hours of IL-1β stimulation. IL-1β-induced CXCL8 protein levels were measured after pretreatment with 100-µM eATP in the presence or absence of CD73 inhibitor. The effect of eATP degradation to adenosine on CXCL8 levels was investigated using agonist and antagonist of adenosine receptors.
RESULTS
Levels of CD39, CD73, and adenosine receptor mRNA were differentially modulated by IL-1β. ATP pretreatment impaired IL-1β-induced CXCL8 secretion and required activation of heme oxygenase-1 (HO-1) and phosphorylated adenosine monophosphate-activated protein kinase (pAMPK). The inhibition of CD73 or the inhibition of adenosine receptors abrogated the ATP effect on CXCL8 secretion.
CONCLUSIONS
CD73-generated adenosine dampens IL-1β-induced CXCL8 in HGFs and involves HO-1 and pAMPK signaling. These results imply that CD73 is a negative regulator of the inflammatory microenvironment, suggesting that this ectoenzyme could be involved in the generation of deficient CXCL8 gradient in chronic inflammation.
Identifiants
pubmed: 31347162
doi: 10.1002/JPER.19-0137
pmc: PMC6980930
mid: NIHMS1043658
doi:
Substances chimiques
Interleukin-1beta
0
Adenosine Monophosphate
415SHH325A
Heme Oxygenase-1
EC 1.14.14.18
Protein Kinases
EC 2.7.-
5'-Nucleotidase
EC 3.1.3.5
Adenosine
K72T3FS567
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
253-262Subventions
Organisme : NIDCR NIH HHS
ID : R01 DE016593
Pays : United States
Informations de copyright
© 2019 American Academy of Periodontology.
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