Role of G-protein-coupled adenosine receptors in downregulation of inflammation and protection from tissue damage View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2001-12

AUTHORS

Akio Ohta, Michail Sitkovsky

ABSTRACT

Inappropriate or prolonged inflammation is the main cause of many diseases; for this reason it is important to understand the physiological mechanisms that terminate inflammation in vivo. Agonists for several Gs-protein-coupled receptors, including cell-surface adenosine purinergic receptors, can increase levels of immunosuppressive cyclic AMP in immune cells; however, it was unknown whether any of these receptors regulates inflammation in vivo. Here we show that A2a adenosine receptors have a non-redundant role in the attenuation of inflammation and tissue damage in vivo. Sub-threshold doses of an inflammatory stimulus that caused minimal tissue damage in wild-type mice were sufficient to induce extensive tissue damage, more prolonged and higher levels of pro-inflammatory cytokines, and death of male animals deficient in the A2a adenosine receptor. Similar observations were made in studies of three different models of inflammation and liver damage as well as during bacterial endotoxin-induced septic shock. We suggest that A2a adenosine receptors are a critical part of the physiological negative feedback mechanism for limitation and termination of both tissue-specific and systemic inflammatory responses. More... »

PAGES

916

Journal

TITLE

Nature

ISSUE

6866

VOLUME

414

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/414916a

DOI

http://dx.doi.org/10.1038/414916a

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1049904447

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/11780065


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