title: Adenosine deaminase in the modulation of immune system and its potential as a novel target for treatment of inflammatory disorders.
abstract: The adenosine pathway is a powerful evolutionarily selected mechanism aimed at a fine modulation of inflammatory responses and protection of tissues from injuries. Adenosine exerts its modulatory effects via interaction with G protein-coupled receptors, designated as A(1), A(2A), A(2B) and A(3). In this regard, extracellular adenosine concentrations are critical in determining its ability of regulating several biological functions. The levels achieved by adenosine in close proximity of its receptors are strictly regulated by a variety of dynamic mechanisms, including intracellular and extracellular biosynthesis, transport and metabolism, based on tissue energy status. In this context, the catabolic enzyme adenosine deaminase (ADA) represents a critical checkpoint in the regulation of extracellular adenosine levels and, consequently, in the control of receptor stimulation, thus playing a pivotal role in the modulation of purinergic responses to several pathophysiological events, such as chronic pulmonary diseases, rheumatoid arthritis, inflammatory bowel diseases and sepsis. This article reviews current data on the role played by ADA in the regulation of immune system activity through its modulation of adenosine pathways. Particular attention has been paid to the involvement of ADA in the pathophysiology of relevant inflammatory diseases. In addition, the interest in designing and developing novel ADA inhibitors, as new tools potentially useful for the therapeutic management of inflammatory disorders, has been discussed.
authors.affiliation: Division of Pharmacology and Chemotherapy, Department of Internal Medicine, University of Pisa, Pisa, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Antonioli
authors.forename: Rocchina
authors.initials: R
authors.lastname: Colucci
authors.forename: Concettina
authors.initials: C
authors.lastname: La Motta
authors.forename: Marco
authors.initials: M
authors.lastname: Tuccori
authors.forename: Oriana
authors.initials: O
authors.lastname: Awwad
authors.forename: Federico
authors.initials: F
authors.lastname: Da Settimo
authors.forename: Corrado
authors.initials: C
authors.lastname: Blandizzi
authors.forename: Matteo
authors.initials: M
authors.lastname: Fornai
mesh_terms: D000241:Adenosine / Q000378:metabolism; D000243:Adenosine Deaminase / Q000187:drug effects* / Q000378:metabolism; D058892:Adenosine Deaminase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use; D015195:Drug Design; D006801:Humans; D007107:Immune System / Q000201:enzymology; D007249:Inflammation / Q000188:drug therapy* / Q000201:enzymology / Q000503:physiopathology; D018047:Receptors, Purinergic P1 / Q000378:metabolism
chemical_list: D058892:Adenosine Deaminase Inhibitors; D000893:Anti-Inflammatory Agents; D018047:Receptors, Purinergic P1; D000243:Adenosine Deaminase; D000241:Adenosine