Critical Role of Hypoxia and A2A Adenosine Receptors in Liver Tissue-Protecting Physiological Anti-Inflammatory Pathway

Choukèr, Alexander; Thiel, Manfred; Lukashev, Dmitriy; Ward, Jerrold M.; Kaufmann, Inès; Apasov, Sergey; Sitkovsky, Michail V.; Ohta, Akio

doi:10.2119/2007-00075.chouker

Cited by 50 publications

(35 citation statements)

References 42 publications

(50 reference statements)

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“…Hereby, the endogenous anti-inflammatory effect of adenosine can be displayed. This is in good accordance with the physiological role of adenosine release as it is mainly triggered by hypoxia (Eltzschig et al, 2004;Chouker et al, 2008). The endogenous adenosine release has hereby the capacity to affect inflammatory responses (Eltzschig and Carmeliet, 2011).…”

Section: Cell Blood Counts As Indicators Of Catecholamine Triggered Isupporting

confidence: 80%

Early Adaption to the Antarctic Environment at Dome C: Consequences on Stress-Sensitive Innate Immune Functions

Feuerecker¹,

Crucian

Salam

et al. 2014

High Altitude Medicine & Biology

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As this early adaptation is not related to psychological stress, the changes observed are likely to be induced by environmental stressors, especially hypoxia. As hypoxia is triggering ATP-catabolism, leading to elevated endogenous adenosine concentrations, this and the increased catecholamine concentration might contribute to the early, but reversible downregulation of innate immune functions. This indicates the slope of innate immune adaptation to hypoxia.

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Section: Cell Blood Counts As Indicators Of Catecholamine Triggered Isupporting

confidence: 80%

Early Adaption to the Antarctic Environment at Dome C: Consequences on Stress-Sensitive Innate Immune Functions

Feuerecker¹,

Crucian

Salam

et al. 2014

High Altitude Medicine & Biology

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“…Activated T cells are known to upregulate adenosine deaminase (ADA), an enzyme capable of metabolizing adenosine to inosine (30). Therefore, strong continuous A2aR signaling from endogenous adenosine sources may only occur under special circumstances such as hypoxia where CD73is up-regulated to facilitate increased extracellular adenosine production in close proximity to A2a receptors (31-33). Going forward, it will be important to identify the immunological context (spatial and temporal) whereby extracellular adenosine counter-regulates Tfh and GC-Tfh differentiation.…”

Section: Discussionmentioning

confidence: 99%

Cutting Edge: Adenosine A2a Receptor Signals Inhibit Germinal Center T Follicular Helper Cell Differentiation during the Primary Response to Vaccination

Schmiel

Yang

Jenkins

et al. 2017

The Journal of Immunology

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Adenosine A2a receptor (A2aR) signaling acts as a barrier to autoimmunity by promoting anergy, inducing regulatory T cells (Tregs), and inhibiting effector T cells. However, in vivo effects of A2aR signaling on polyclonal CD4 T cells during a primary response to foreign antigen has yet to be determined. To address this problem, we immunized mice with peptide antigen 2W1S coupled to PE in CFA and treated with the selective A2aR agonist CGS-21680 (CGS). 2W1S:I-Ab-specific tetramer-binding CD4 T cells did not become anergic or differentiate into Foxp3+ Tregs. Additionally, CGS treatment did not inhibit Th1 or Th17 differentiation. However, CGS did abrogate germinal center (GC) T follicular helper (Tfh) cells, and blunted PE-specific GC B cell responses. The use of A2aR-deficientCD4 T cells established that this CGS effect was T cell-intrinsic. Therefore, this study has identified a unique role for A2aRs in regulating CD4 T cell differentiation during vaccination.

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“…Ethanol, which is metabolized as a lipid and requires ATP hydrolysis in order to be metabolized to acetyl-CoA, also causes adenosine release as a result of ATP breakdown 156,164-167 . More recently, it has been appreciated that extracellular adenosine levels might reach extremely high concentrations in the setting of rapid cellular breakdown and hypoxia, such as occurs in tumours, leading to consequences such as immunosuppression by tumours 101,102,168 .…”

Section: Regulation Of Extracellular Adenosinementioning

confidence: 99%

Adenosine and adenosine receptors in the pathogenesis and treatment of rheumatic diseases

Cronstein¹,

2016

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Adenosine, a nucleoside derived primarily from the extracellular hydrolysis of adenine nucleotides, is a potent regulator of inflammation. Adenosine mediates its effects on inflammatory cells by engaging one or more cell-surface receptors. The expression and function of adenosine receptors on different cell types change during the course of rheumatic diseases, such as rheumatoid arthritis. Targeting adenosine receptors directly for the treatment of rheumatic diseases is currently under study; however, indirect targeting of adenosine receptors by enhancing adenosine levels at inflamed sites accounts for most of the anti-inflammatory effects of methotrexate, the anchor drug for the treatment of rheumatoid arthritis. In this Review, we discuss the regulation of extracellular adenosine levels and the role of adenosine in regulating the inflammatory and immune responses in rheumatic diseases such as Rheumatoid Arthritis, psoriasis and other types of inflammatory arthritis. In addition, adenosine and its receptors are involved in promoting fibrous matrix production in the skin and other organs and the role of adenosine in fibrosis and fibrosing diseases will also be discussed.

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Critical Role of Hypoxia and A2A Adenosine Receptors in Liver Tissue-Protecting Physiological Anti-Inflammatory Pathway

Cited by 50 publications

References 42 publications

Early Adaption to the Antarctic Environment at Dome C: Consequences on Stress-Sensitive Innate Immune Functions

Early Adaption to the Antarctic Environment at Dome C: Consequences on Stress-Sensitive Innate Immune Functions

Cutting Edge: Adenosine A2a Receptor Signals Inhibit Germinal Center T Follicular Helper Cell Differentiation during the Primary Response to Vaccination

Adenosine and adenosine receptors in the pathogenesis and treatment of rheumatic diseases

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