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Hypoxia/Reoxygenation Inhibits P2Y11 Receptor Expression and Its Immunosuppressive Activity in Human Dendritic Cells
- Source :
- Journal of Immunology, Journal of Immunology, Publisher : Baltimore : Williams & Wilkins, c1950-. Latest Publisher : Bethesda, MD : American Association of Immunologists, 2015, 195 (2), pp.651-660. ⟨10.4049/jimmunol.1500197⟩, Journal of Immunology, 2015, 195 (2), pp.651-660. ⟨10.4049/jimmunol.1500197⟩
- Publication Year :
- 2015
-
Abstract
- High concentrations of extracellular ATP (eATP) resulting from cell damage may be found during an ischemia/reperfusion (I/R) episode at the site of injury. eATP activates purinergic receptors in dendritic cells (DCs) and may inhibit inflammation. This immunosuppressive activity could be of interest in the field of I/R, which is an inflammatory condition involved in myocardial infarction, stroke, and solid organ transplantation. However, the specific purinergic receptor responsible for this effect remains to be identified. In this study, we report that eATP induced maturation of human monocyte-derived DCs. Additionally, eATP inhibited IL-12 production whereas IL-10 levels remained unchanged in activated DCs. These effects were prevented by the P2Y11R antagonist NF340. Interestingly, a 5-h hypoxia prevented the effects of eATP on cytokine production whereas a 1-h hypoxia did not affect the eATP-mediated decrease of IL-12 and IL-6. We showed a time-dependent downregulation of P2Y11R at both mRNA and protein levels that was prevented by knocking down hypoxia-inducible factor-1α. In this study, we showed an immunosuppressive role of P2Y11R in human DCs. Additionally, we demonstrated that the time-dependent downregulation of P2Y11R by hypoxia orientates DCs toward a proinflammatory phenotype that may be involved in post-I/R injuries as observed after organ transplantation.
- Subjects :
- Time Factors
[SDV.IMM] Life Sciences [q-bio]/Immunology
Purinergic Antagonists
Transcription, Genetic
medicine.medical_treatment
Receptor expression
Immunology
Primary Cell Culture
Inflammation
[SDV.BC]Life Sciences [q-bio]/Cellular Biology
Pharmacology
Biology
Proinflammatory cytokine
03 medical and health sciences
0302 clinical medicine
Adenosine Triphosphate
Downregulation and upregulation
medicine
Immunology and Allergy
Humans
RNA, Small Interfering
Receptor
[SDV.BC] Life Sciences [q-bio]/Cellular Biology
030304 developmental biology
Immunosuppression Therapy
0303 health sciences
Interleukin-6
Receptors, Purinergic P2
Purinergic receptor
Dendritic Cells
Hypoxia-Inducible Factor 1, alpha Subunit
Interleukin-12
Cell Hypoxia
Interleukin-10
Oxygen
Cytokine
Gene Expression Regulation
030220 oncology & carcinogenesis
[SDV.IMM]Life Sciences [q-bio]/Immunology
Signal transduction
medicine.symptom
Signal Transduction
Subjects
Details
- ISSN :
- 15506606 and 00221767
- Volume :
- 195
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Accession number :
- edsair.doi.dedup.....edb8c43857c707c2a7db4529540131af