ArticleAmerican journal of respiratory cell and molecular biology2013
Repression of the equilibrative nucleoside transporters dampens inflammatory lung injury.
Article in American journal of respiratory cell and molecular biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 35 citations in OpenAlex.
- Article
- Addressing the Clinical Importance of Equilibrative Nucleoside Transporters in Drug Discovery and Development.Clinical pharmacology and therapeutics · 2023Review
- Targeting myocardial equilibrative nucleoside transporter ENT1 provides cardioprotection by enhancing myeloid Adora2b signaling.JCI insight · 2023Article
- SARS-CoV-2 infection dysregulates the expression of clinically relevant drug metabolizing enzymes in Vero E6 cells and membrane transporters in human lung tissues.Frontiers in pharmacology · 2023Article
- Article
- The Hypoxia-Adenosine Link during Myocardial Ischemia-Reperfusion Injury.Biomedicines · 2022Review
- PF-07321332 (Nirmatrelvir) does not interact with human ENT1 or ENT2: Implications for COVID-19 patients.Clinical and translational science · 2022Article
- Response to Comments on "Remdesivir and EIDD-1931 Interact with Human Equilibrative Nucleoside Transporters 1 and 2: Implications for Reaching SARS-CoV-2 Viral Sanctuary Sites".Molecular pharmacology · 2022Article
- Alternative adenosine Receptor activation: The netrin-Adora2b link.Frontiers in pharmacology · 2022Review
- Emerging roles of dysregulated adenosine homeostasis in brain disorders with a specific focus on neurodegenerative diseases.Journal of biomedical science · 2021Review
- Enhancing Extracellular Adenosine Levels Restores Barrier Function in Acute Lung Injury Through Expression of Focal Adhesion Proteins.Frontiers in molecular biosciences · 2021Article
- Adenosine at the Interphase of Hypoxia and Inflammation in Lung Injury.Frontiers in immunology · 2020Review
- Equilibrative Nucleoside Transporter 2: Properties and Physiological Roles.BioMed research international · 2020Review
- Possible Role of Adenosine in COVID-19 Pathogenesis and Therapeutic Opportunities.Frontiers in pharmacology · 2020Article
- Blockade of equilibrative nucleoside transporter 1/2 protects against Pseudomonas aeruginosa-induced acute lung injury and NLRP3 inflammasome activation.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020Article
- Purinergic Signaling in Pulmonary Inflammation.Frontiers in immunology · 2019Review
- Coordination of ENT2-dependent adenosine transport and signaling dampens mucosal inflammation.JCI insight · 2018Article
- Changes in aortic reactivity associated with the loss of equilibrative nucleoside transporter 1 (ENT1) in mice.PloS one · 2018Article
- Whole-Exome Sequencing Identifies the 6q12-q16 Linkage Region and a Candidate Gene, TTK, for Pulmonary Nontuberculous Mycobacterial Disease.American journal of respiratory and critical care medicine · 2017Article
- Equilibrative nucleoside transporters-A review.Nucleosides, nucleotides & nucleic acids · 2017Review
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
Acute lung injury (ALI) is a devastating disorder of the lung that is characterized by hypoxemia, overwhelming pulmonary inflammation, and a high mortality in the critically ill. Adenosine has been implicated as an anti-inflammatory signaling molecule, and previous studies showed that extracellular adenosine concentrations are increased in inflamed tissues. Adenosine signaling is terminated by the uptake of adenosine from the extracellular into the intracellular compartment via equilibrative nucleoside transporters (ENTs). However, their role in controlling adenosine signaling during pulmonary inflammation remains unknown. After inflammatory in vitro experiments, we observed a repression of ENT1 and ENT2 that was associated with an attenuation of extracellular adenosine uptake. Experiments using short, interfering RNA silencing confirmed a significant contribution of ENT repression in elevating extracellular adenosine concentrations during inflammation. Furthermore, an examination of the ENT2 promoter implicated NF-κB as a key regulator for the observed ENT repression. Additional in vivo experiments using a murine model of inflammatory lung injury showed that the pharmacological inhibition of ENT1 and ENT2 resulted in improved pulmonary barrier function and reduced signs of acute inflammation of the lung. Whereas experiments on Ent1(-/-) or Ent2(-/-) mice revealed lung protection in LPS-induced lung injury, an examination of bone marrow chimeras for ENTs pointed to the nonhematopoetic expression of ENTs as the underlying cause of dampened pulmonary inflammation during ALI. Taken together, these findings reveal the transcriptional repression of ENTs as an innate protective response during acute pulmonary inflammation. The inhibition of ENTs could be pursued as a therapeutic option to ameliorate inflammatory lung injury.
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