Adenosine signaling during acute and chronic disease states
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TLDR
Key observations are discussed that define the beneficial and detrimental aspects of adenosine signaling during acute and chronic disease states with an emphasis on cellular processes, such as inflammatory cell regulation, vascular barrier function, and tissue fibrosis.Abstract:
Adenosine is a signaling nucleoside that is produced following tissue injury, particularly injury involving ischemia and hypoxia. The production of extracellular adenosine and its subsequent signaling through adenosine receptors plays an important role in orchestrating injury responses in multiple organs. There are four adenosine receptors that are widely distributed on immune, epithelial, endothelial, neuronal,and stromal cells throughout the body. Interestingly, these receptors are subject to altered regulation following injury. Studies in mouse models and human cells and tissues have identified that the production of adenosine and its subsequent signaling through its receptors plays largely beneficial roles in acute disease states, with the exception of brain injury. In contrast, if elevated adenosine levels are sustained beyond the acute injury phase, adenosine responses can become detrimental by activating pathways that promote tissue injury and fibrosis. Understanding when during the course of disease adenosine signaling is beneficial as opposed to detrimental and defining the mechanisms involved will be critical for the advancement of adenosine-based therapies for acute and chronic diseases. The purpose of this review is to discuss key observations that define the beneficial and detrimental aspects of adenosine signaling during acute and chronic disease states with an emphasis on cellular processes, such as inflammatory cell regulation, vascular barrier function, and tissue fibrosis.read more
Citations
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Paulina Navon Elkan,Sarah B. Pierce,Reeval Segel,Reeval Segel,Tom Walsh,Judith Barash,Shai Padeh,Abraham Zlotogorski,Yackov Berkun,Joseph J. Press,Mukamel M,Isabel Voth,Philip J. Hashkes,Liora Harel,Vered Hoffer,Eduard Ling,Fatoş Yalçınkaya,Ozgur Kasapcopur,Ming K. Lee,Rachel E. Klevit,Paul Renbaum,Ariella Weinberg-Shukron,Ariella Weinberg-Shukron,Elif Funda Sener,Elif Funda Sener,Barbara Schormair,Sharon Zeligson,Dina Marek-Yagel,Tim M. Strom,Mordechai Shohat,Mordechai Shohat,Amihood Singer,Alan Rubinow,Elon Pras,Juliane Winkelmann,Juliane Winkelmann,Mustafa Tekin,Yair Anikster,Mary Claire King,Ephrat Levy-Lahad,Ephrat Levy-Lahad +40 more
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TL;DR: It is shown for the first time that extracellularAdenosine activates the NLRP3 inflammasome by two ways: by interacting with adenosine receptors at nanomolar/micromolar concentrations and through cellular uptake by equilibrative nucleoside transporters at millimolar concentrations.
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Itsaso Montalbán del Barrio,Cornelia Penski,Cornelia Penski,Laura Schlahsa,Roland Stein,J Diessner,Achim Wöckel,Johannes Dietl,Manfred B. Lutz,Michel Mittelbronn,Michel Mittelbronn,Jörg Wischhusen,Sebastian Häusler +12 more
TL;DR: Adenosine generated by OvCA cells likely contributes to the recruitment of TAMs which further amplify adenosine-dependent immunosuppression via additional ectonucleotidase activity, which could improve immune responses in ovarian cancer.
References
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Book ChapterDOI
Adenosine Receptors and Inflammation
TL;DR: The potent effects of adenosine signaling on the regulation of inflammation suggest that targeting specificadenosine receptor activation or inactivation using selective agonists and antagonists could have important therapeutic implications in numerous diseases.
Journal ArticleDOI
Adenosine signaling contributes to ethanol-induced fatty liver in mice
Zhongsheng Peng,Pier Andrea Borea,Tuere Wilder,Herman Yee,Luis Chiriboga,Michael R. Blackburn,G. Azzena,Giuseppe Resta,Bruce N. Cronstein +8 more
TL;DR: Results indicate that adenosine generated by ethanol metabolism plays an important role in ethanol-induced hepatic steatosis via both A1 and A2B receptors and suggest that targeting adenosines receptors may be effective in the prevention of alcohol-induced fatty liver.
Journal ArticleDOI
Excess adenosine in murine penile erectile tissues contributes to priapism via A2B adenosine receptor signaling
Tiejuan Mi,Shahrzad Abbasi,Hong Zhang,Karen S. Uray,Janci L. Chunn,Ling Wei Xia,Jose G. Molina,Norman W. Weisbrodt,Rodney E. Kellems,Michael R. Blackburn,Yang Xia +10 more
TL;DR: It is shown that excessive adenosine accumulation in the penis contributes to priapism through increased A2BR signaling in both Ada -/- and SCD transgenic mice, and it is suggested that strategies to either reduceAdenosine or block A2 BR activation may prove beneficial in the treatment of this disorder.
Journal ArticleDOI
Adenosine A2A receptor activation attenuates inflammation and injury in diabetic nephropathy.
Alaa S. Awad,Liping Huang,Hong Ye,Elizabeth Thu Anh Duong,W. Kline Bolton,Joel Linden,Mark D. Okusa +6 more
TL;DR: It is demonstrated that chronic A(2A)R activation in diabetic rats ameliorates histological and functional changes in kidneys induced by diabetes and causes reduced inflammation associated with diabetic nephropathy.
Journal ArticleDOI
Adenosine A2A receptors induced on iNKT and NK cells reduce pulmonary inflammation and injury in mice with sickle cell disease.
Kori L. Wallace,Joel Linden +1 more
TL;DR: Activation of induced A(2A)Rs on iNKT and NK cells in SCD mice is sufficient to improve baseline pulmonary function and prevent hypoxia-reoxygenation-induced exacerbation of pulmonary injury.