Dataset Information

Short-Term Hypoxia Dampens Inflammation in vivo via Enhanced Adenosine Release and Adenosine 2B Receptor Stimulation.

ABSTRACT: Hypoxia and inflammation are closely intertwined phenomena. Critically ill patients often suffer from systemic inflammatory conditions and concurrently experience short-lived hypoxia. We evaluated the effects of short-term hypoxia on systemic inflammation, and show that it potently attenuates pro-inflammatory cytokine responses during murine endotoxemia. These effects are independent of hypoxia-inducible factors (HIFs), but involve augmented adenosine levels, in turn resulting in an adenosine 2B receptor-mediated post-transcriptional increase of interleukin (IL)-10 production. We translated our findings to humans using the experimental endotoxemia model, where short-term hypoxia resulted in enhanced plasma concentrations of adenosine, augmentation of endotoxin-induced circulating IL-10 levels, and concurrent attenuation of the pro-inflammatory cytokine response. Again, HIFs were shown not to be involved. Taken together, we demonstrate that short-term hypoxia dampens the systemic pro-inflammatory cytokine response through enhanced purinergic signaling in mice and men. These effects may contribute to outcome and provide leads for immunomodulatory treatment strategies for critically ill patients.

SUBMITTER: Kiers D

PROVIDER: S-EPMC6085583 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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Short-Term Hypoxia Dampens Inflammation in vivo via Enhanced Adenosine Release and Adenosine 2B Receptor Stimulation.

Kiers Dorien D Wielockx Ben B Peters Esther E van Eijk Lucas T LT Gerretsen Jelle J John Aaron A Janssen Emmy E Groeneveld Rianne R Peters Mara M Damen Lars L Meneses Ana M AM Krüger Anja A Langereis Jeroen D JD Zomer Aldert L AL Blackburn Michael R MR Joosten Leo A LA Netea Mihai G MG Riksen Niels P NP van der Hoeven Johannes G JG Scheffer Gert-Jan GJ Eltzschig Holger K HK Pickkers Peter P Kox Matthijs M

EBioMedicine 20180704

Hypoxia and inflammation are closely intertwined phenomena. Critically ill patients often suffer from systemic inflammatory conditions and concurrently experience short-lived hypoxia. We evaluated the effects of short-term hypoxia on systemic inflammation, and show that it potently attenuates pro-inflammatory cytokine responses during murine endotoxemia. These effects are independent of hypoxia-inducible factors (HIFs), but involve augmented adenosine levels, in turn resulting in an adenosine 2B ...[more]

PMID: 29983349

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Dataset Information

Short-Term Hypoxia Dampens Inflammation in vivo via Enhanced Adenosine Release and Adenosine 2B Receptor Stimulation.

Publications

Short-Term Hypoxia Dampens Inflammation in vivo via Enhanced Adenosine Release and Adenosine 2B Receptor Stimulation.

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