2.50
HDL Handle:
http://hdl.handle.net/10033/203609
Title:
Adenosine in the inflamed gut: a Janus faced compound.
Authors:
Estrela, A B; Abraham, W-R
Abstract:
The purine ribonucleoside adenosine (Ado) has been recognized for its regulatory functions in situations of cellular stress like ischemia, hypoxia and inflammation. The importance of extracellular Ado as a modulator in the immune system is a theme of great appreciation and the focus of recent increasing interest in the field of gastrointestinal inflammation. In this review, the different aspects of Ado signaling during inflammatory responses in the gut are discussed, considering the contribution of the four known Ado receptors (ARs; A(1), A(2A), A(2B), and A(3)), their mechanisms and expression patterns. Activation of these receptors in epithelial cells as well as in immune cells recruited to the inflamed intestinal mucosa determines the overall effect, ranging from a protective, anti-inflammatory modulation to a strong pro-inflammatory induction. Here we present the current advances in agonists and antagonists development and their potential therapeutic application studied in animal models of intestinal inflammation. In addition, alternative complementary approaches to manipulate such a complex signaling system are discussed, for example, the use of AR allosteric modulators or interference with Ado metabolism. Special features of the gut environment are taken into account: the contribution of diet components; the involvement of Ado in intestinal infections; the interactions with the gut microbiome, particularly, the recent exciting finding that an intestinal bacterium can directly produce extracellular Ado in response to host defense mechanisms in an inflammation scenario. Understanding each component of this dynamic system will broaden the possibilities for applying Ado signaling as a therapeutic target in gut inflammation.
Affiliation:
Helmholtz Center for Infection Research, Chemical Microbiology, Inhoffenstrasse 7, 38124 Braunschweig, Germany.
Citation:
Adenosine in the inflamed gut: a Janus faced compound. 2011, 18 (18):2791-815 Curr. Med. Chem.
Journal:
Current medicinal chemistry
Issue Date:
2011
URI:
http://hdl.handle.net/10033/203609
PubMed ID:
21649583
Language:
en
ISSN:
1875-533X
Appears in Collections:
Publications of RG Chemical Microbiology (CMIK)

Full metadata record

DC FieldValueLanguage
dc.contributor.authorEstrela, A Ben
dc.contributor.authorAbraham, W-Ren
dc.date.accessioned2012-01-18T15:07:35Z-
dc.date.available2012-01-18T15:07:35Z-
dc.date.issued2011-
dc.identifier.citationAdenosine in the inflamed gut: a Janus faced compound. 2011, 18 (18):2791-815 Curr. Med. Chem.en
dc.identifier.issn1875-533X-
dc.identifier.pmid21649583-
dc.identifier.urihttp://hdl.handle.net/10033/203609-
dc.description.abstractThe purine ribonucleoside adenosine (Ado) has been recognized for its regulatory functions in situations of cellular stress like ischemia, hypoxia and inflammation. The importance of extracellular Ado as a modulator in the immune system is a theme of great appreciation and the focus of recent increasing interest in the field of gastrointestinal inflammation. In this review, the different aspects of Ado signaling during inflammatory responses in the gut are discussed, considering the contribution of the four known Ado receptors (ARs; A(1), A(2A), A(2B), and A(3)), their mechanisms and expression patterns. Activation of these receptors in epithelial cells as well as in immune cells recruited to the inflamed intestinal mucosa determines the overall effect, ranging from a protective, anti-inflammatory modulation to a strong pro-inflammatory induction. Here we present the current advances in agonists and antagonists development and their potential therapeutic application studied in animal models of intestinal inflammation. In addition, alternative complementary approaches to manipulate such a complex signaling system are discussed, for example, the use of AR allosteric modulators or interference with Ado metabolism. Special features of the gut environment are taken into account: the contribution of diet components; the involvement of Ado in intestinal infections; the interactions with the gut microbiome, particularly, the recent exciting finding that an intestinal bacterium can directly produce extracellular Ado in response to host defense mechanisms in an inflammation scenario. Understanding each component of this dynamic system will broaden the possibilities for applying Ado signaling as a therapeutic target in gut inflammation.en
dc.language.isoenen
dc.subject.meshAdenosineen
dc.subject.meshAdrenergic Agonistsen
dc.subject.meshAdrenergic Antagonistsen
dc.subject.meshAnimalsen
dc.subject.meshHumansen
dc.subject.meshInflammatory Bowel Diseasesen
dc.subject.meshReceptors, Purinergic P1en
dc.subject.meshStructure-Activity Relationshipen
dc.titleAdenosine in the inflamed gut: a Janus faced compound.en
dc.contributor.departmentHelmholtz Center for Infection Research, Chemical Microbiology, Inhoffenstrasse 7, 38124 Braunschweig, Germany.en
dc.identifier.journalCurrent medicinal chemistryen

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