Adenosine as an Endogenous Mediator of Hypoxia for Induction of Vascular Endothelial Growth Factor mRNA in U-937 Cells

Hashimoto, Etsuo; Kage, Kumie; Ogita, Tadaatsu; Nakaoka, Takashi; Matsuoka, Ryo; Kira, Yuji

doi:10.1006/bbrc.1994.2462

Cited by 66 publications

(32 citation statements)

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“…On the basis of our findings in vivo, we can speculate that alterations of adenosine levels in vivo interfere with VEGF-mediated endothelial cell survival and hence have an impact on vascular integrity. Adenosine is an important regulator of VEGF expression (19,34); however, its effects are determined by cell type and specific adenosine receptor engagement (19,34,40). Preliminary findings in ADAdeficient lungs suggest upregulation of A 3 and A 2B receptors in the bronchial epithelium (M. R. Blackburn, unpublished observations).…”

Section: Discussionmentioning

confidence: 99%

Gene expression profiling in inflammatory airway disease associated with elevated adenosine

Banerjee

Young

Volmer

et al. 2002

American Journal of Physiology-Lung Cellular and Molecular Phys

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Adenosine has been implicated as a modulator of inflammatory processes central to asthma. However, the molecular mechanisms involved are poorly understood. We used Atlas mouse cDNA arrays to analyze differential gene expression in association with lung inflammation resulting from elevated adenosine in adenosine deaminase (ADA)-deficient mice. We report that of the 1,176 genes on the array, the expression patterns of 280 genes were consistently altered. Of these genes, the steady-state levels of 93 genes were upregulated and 29 were downregulated. We also show that lowering adenosine levels with ADA enzyme therapy has striking effects on gene expression that may be associated with resolution of pulmonary eosinophilia. In addition, we confirmed the nucleic acid and protein expression of vascular endothelial growth factor and monocyte chemoattractant protein-3, two candidate genes that may be regulated by adenosine. In conclusion, high-throughput profiling of gene expression by cDNA array hybridization has provided an overview of critical regulatory genes involved in airway inflammation in ADA-deficient mice. These mice will serve as a useful in vivo model for characterizing molecular mechanisms of adenosine-mediated lung damage.

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Section: Discussionmentioning

confidence: 99%

Gene expression profiling in inflammatory airway disease associated with elevated adenosine

Banerjee

Young

Volmer

et al. 2002

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…Thus, hypoxia enhances VEGF expression in monocytes as well as a variety of other cell types, including fibroblasts, keratinocytes, myocytes, and endothelial cells 38,[97][98][99] . Adenosine has been shown to mediate this hypoxic response 100,101 , and subsequent transduction pathways increase both VEGF mRNA transcription and half-life [102][103][104] .…”

Section: Hypoxia Induces Vegfmentioning

confidence: 99%

The Role of Vascular Endothelial Growth Factor in Wound Healing

Bao

Kodra

Tomic‐Canic

et al. 2009

Journal of Surgical Research

940

732

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“…Stimulation of A 2 receptors in U-937 human macrophages elicits VEGF mRNA accumulation (Hashimoto et al, 1994). Moreover, hypoxia, which is a major trigger of VEGF expression in most cell types (Semenza, 2003), augmented VEGF mRNA expression in U-937 cells, a process that could be prevented by adenosine deaminase and DMPX, indicating that hypoxia triggers the release of adenosine and the adenosine released so increases VEGF mRNA abundance.…”

Section: Adenosine Regulates Vascular Endothelial Growth Factor Produmentioning

confidence: 99%

Shaping of monocyte and macrophage function by adenosine receptors

Haskó

Pacher

Deitch

et al. 2007

Pharmacology & Therapeutics

194

154

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Adenosine is an endogenous purine nucleoside that, following its release into the extracellular space, binds to specific adenosine receptors expressed on the cell surface. Adenosine appears in the extracellular space under metabolically stressful conditions, which are associated with ischemia, inflammation, and cell damage. There are 4 types of adenosine receptors (A 1 , A 2A , A 2B and A 3 ) and all adenosine receptors are members of the G protein-coupled family of receptors. Adenosine receptors are expressed on monocytes and macrophages and through these receptors adenosine modulates monocyte and macrophage function. Since monocytes and macrophages are activated by the same danger signals that cause accumulation of extracellular adenosine, adenosine receptors expressed on macrophages represent a sensor system that provide monocytes and macrophages with information about the stressful environment. Adenosine receptors, thus, allow monocytes and macrophages to fine-tune their responses to stressful stimuli. Here, we review the consequences of adenosine receptor activation on monocyte/macrophage function. We will detail the effect of stimulating the various adenosine receptor subtypes on macrophage differentiation/proliferation, phagocytosis, and tissue factor (TF) expression. We will also summarize our knowledge of how adenosine impacts the production of extracellular mediators secreted by monocytes and macrophages in response to toll-like receptor (TLR) ligands and other inflammatory stimuli. Specifically, we will delineate how adenosine affects the production of superoxide, nitric oxide (NO), tumor necrosis factor-α, interleukin (IL)-12, IL-10, and vascular endothelial growth factor (VEGF). A deeper insight into the regulation of monocyte and macrophage function by adenosine receptors should assist in developing new therapies for inflammatory diseases.

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Adenosine as an Endogenous Mediator of Hypoxia for Induction of Vascular Endothelial Growth Factor mRNA in U-937 Cells

Cited by 66 publications

References 0 publications

Gene expression profiling in inflammatory airway disease associated with elevated adenosine

Gene expression profiling in inflammatory airway disease associated with elevated adenosine

The Role of Vascular Endothelial Growth Factor in Wound Healing

Shaping of monocyte and macrophage function by adenosine receptors

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