The hypoxia-adenosine link during inflammation

Bowser, Jessica L.; Lee, Jae Woo; Yuan, Xiaoyi; Eltzschig, Holger K.

doi:10.1152/japplphysiol.00101.2017

Cited by 98 publications

(87 citation statements)

References 146 publications

(239 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…With tissue damage, inflammation, and hypoxic stress, ATP is released from stressed, necrotic, and/or apoptotic cells and is hydrolyzed stepwise by ectonucleoside triphosphate diphosphohydrolase-1 (CD39), converting ATP to AMP, and CD73, converting AMP to extracellular adenosine (Figure 1). ATP's activation of ATP receptors promotes inflammation, whereas subsequent breakdown of ATP to extracellular adenosine and activation of adenosine receptors dampens inflammation (Figure 1) (45)(46)(47). Extracellular adenosine signals though four adenosine receptors: A1R, A2AR, A2BR, and A3R (48).…”

Section: Cd73 and Adenosine Receptor Activity Promotes Immunosuppressionmentioning

confidence: 99%

“…In these preclinical studies, extracellular adenosine levels and CD39, CD73, A2AR, and A2BR gene expression decreases and coincides with increased antitumor immunity (102,108). Hypoxiainducible factors (HIFs) are strongly linked to increasing CD73 (109), A2AR (110), and A2BR (111) gene expression and collaborates to increase extracellular adenosine/adenosine receptor signaling for dampening inflammation (46,47). Interestingly, recent studies show tumor cells can reprogram NK cells to gain immunosuppressive functions [e.g., increase IL-10 and transforming growth factor-β (TGF-β) production via signal transducer and activator of transcription 3 (STAT3) transcriptional activity, suppressing IFN-γ production] (112).…”

Section: Natural Killer Cellsmentioning

confidence: 99%

See 1 more Smart Citation

CD73's Potential as an Immunotherapy Target in Gastrointestinal Cancers

et al. 2020

Self Cite

View full text Add to dashboard Cite

CD73, a cell surface 5 ′ nucleotidase that generates adenosine, has emerged as an attractive therapeutic target for reprogramming cancer cells and the tumor microenvironment to dampen antitumor immune cell evasion. Decades of studies have paved the way for these findings, starting with the discovery of adenosine signaling, particularly adenosine A2A receptor (A2AR) signaling, as a potent suppressor of tissue-devastating immune cell responses, and evolving with studies focusing on CD73 in breast cancer, melanoma, and non-small cell lung cancer. Gastrointestinal (GI) cancers are a major cause of cancer-related deaths. Evidence is mounting that shows promise for improving patient outcomes through incorporation of immunomodulatory strategies as single agents or in combination with current treatment options. Recently, several immune checkpoint inhibitors received FDA approval for use in GI cancers; however, clinical benefit is limited. Investigating molecular mechanisms promoting immunosuppression, such as CD73, in GI cancers can aid in current efforts to extend the efficacy of immunotherapy to more patients. In this review, we discuss current clinical and basic research studies on CD73 in GI cancers, including gastric, liver, pancreatic, and colorectal cancer, with special focus on the potential of CD73 as an immunotherapy target in these cancers. We also present a summary of current clinical studies targeting CD73 and/or A2AR and combination of these therapies with immune checkpoint inhibitors.

show abstract

Section: Cd73 and Adenosine Receptor Activity Promotes Immunosuppressionmentioning

confidence: 99%

Section: Natural Killer Cellsmentioning

confidence: 99%

CD73's Potential as an Immunotherapy Target in Gastrointestinal Cancers

et al. 2020

Self Cite

View full text Add to dashboard Cite

show abstract

Section: Functional Roles Of Myeloid Mir‐223 During Inflammatory Disementioning

confidence: 99%

“…IBD, including Crohn's disease and ulcerative colitis, are characterized by disrupted epithelial barrier function, increased bacterial translocation and dysregulated immunological environment in the gut. [75][76][77][78][79][80][81][82][83] Adaptive immunity, Th17 responses especially, plays a crucial role in the propagation of inflammation during IBD. 84,85 On the other hand, dendritic cell (DC) and macrophages are also crucial in the maintenance of intestinal immune homeostasis.…”

Section: Mir-223 In Inflammatory Bowel Diseasesmentioning

confidence: 99%

MicroRNA miR-223 as regulator of innate immunity

Yuan

Berg

Lee

et al. 2018

Journal of Leukocyte Biology

Self Cite

134

105

View full text Add to dashboard Cite

MicroRNAs were discovered more than 2 decades ago and have profound impact on diverse biological processes. Specific microRNAs have important roles in modulating the innate immune response and their dysregulation has been demonstrated to contribute to inflammatory diseases. MiR-223 in particular, is very highly expressed and tightly regulated in hematopoietic cells. It functions as key modulator for the differentiation and activation of myeloid cells. The central role of miR-223 in myeloid cells, especially neutrophil and macrophage differentiation and activation has been studied extensively. MiR-223 contributes to myeloid differentiation by enhancing granulopoiesis while inhibiting macrophage differentiation. Uncontrolled myeloid activation has detrimental consequences in inflammatory disease. MiR-223 serves as a negative feedback mechanism controlling excessive innate immune responses in the maintenance of myeloid cell homeostasis. This review summarizes several topics covering the function of miR-223 in myeloid differentiation, neutrophil and macrophage functions, as well as in inflammatory diseases including acute respiratory distress syndrome and inflammatory bowel disease. In addition, nonmyeloid functions of miR-223 are also discussed in this review. Therapeutic enhancement of miR-223 to dampen inflammatory targets is also highlighted as potential treatment to control excessive innate immune responses during mucosal inflammation.

show abstract

“…There is a lot of literature showed that hypoxia is an independent contributing factor to acute lung injury. Moreover, hypoxia can induce the body's in ammatory response, and in ammation can lead to tissue hypoxia, the two are intertwined, and in uence each other, causing acute lung injury [15][16][17][18] . Hypoxia environment has great in uence on the function of mitochondria.…”

Section: Introductionmentioning

confidence: 99%

Simulated Aeromedical Evacuation Exacerbates Burn Induced Lung Injury: Targeting Mitochondrial DNA for Reversal

Xiao

Zou

et al. 2020

Preprint

View full text Add to dashboard Cite

Abstract Background: Aeromedical evacuation of patients with burn trauma is an important transport method at both wartime and peacetime, which exposes patients to prolonged periods of hypobaric hypoxia. However, the effects of such exposure on burn injury, particularly on burn induced lung injury are largely unexplored. The objective of this study is to investigate the effect of hypobaric hypoxia on burn induced lung injury and to discuss the possible mechanism by using a rat burn model. Methods: Male wistar rats inflicted with 30% total body surface area burn were exposed to hypobaric hypoxia condition (simulated 2000m altitude) or normoxia control for 24 h. Deoxyribonuclease I was systemically administrated as treatment intervention. Systemic inflammatory mediators and mitochondrial deoxyribonucleic acid level were detected. The histopathological examination, and acute lung injury score were determined. Malonaldehyde content, myeloperoxidase activity, and the nucleotide-binding oligomerization domain-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome level in the lung tissue were measured. Data among groups were compared by using analysis of variance followed by the post hoc analysis of Tukey's test. Results: Burn resulted in remarkably higher level of systemic inflammatory cytokines and mitochondrial deoxyribonucleic acid release, which was further heightened by hypobaric hypoxia exposure. Moreover, hypobaric hypoxia exposure gave rise to increased NLRP3 inflammasome expression, elevated malonaldehyde content and myeloperoxidase activity in the lung. Burn induced lung injury was exacerbated as shown by histopathological examination and acute lung injury score. Administration of deoxyribonuclease I markedly reduced mitochondrial deoxyribonucleic acid release and systemic inflammatory cytokines production. Furthermore, NLRP3 inflammasome level in the lung tissue was decreased and burn induced lung injury was ameliorated. Conclusions: Our results suggested that simulated aeromedical evacuation further increased the burn induced mitochondrial deoxyribonucleic acid release and exacerbated burn induced inflammation and lung injury. Deoxyribonuclease I reduced the release of mitochondrial deoxyribonucleic acid and limited the mitochondrial deoxyribonucleic acid-induced systemic inflammation, ameliorated burn-induced acute lung injury. Intervening mitochondrial deoxyribonucleic acid level could be a potential target to protect from burn-induced lung injury during aeromedical conditions and provide with safer air evacuations for severely burned patients.

show abstract

The hypoxia-adenosine link during inflammation

Cited by 98 publications

References 146 publications

CD73's Potential as an Immunotherapy Target in Gastrointestinal Cancers

CD73's Potential as an Immunotherapy Target in Gastrointestinal Cancers

MicroRNA miR-223 as regulator of innate immunity

Simulated Aeromedical Evacuation Exacerbates Burn Induced Lung Injury: Targeting Mitochondrial DNA for Reversal

Contact Info

Product

Resources

About