Immune cell regulation by autocrine purinergic signalling

Nature reviews. Immunology, Год журнала: 2011, Номер 11(3), С. 201 - 212

Опубликована: Фев. 18, 2011

Язык: Английский

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Caspase-8 Blocks Kinase RIPK3-Mediated Activation of the NLRP3 Inflammasome

Immunity, Год журнала: 2012, Номер 38(1), С. 27 - 40

Опубликована: Дек. 20, 2012

Язык: Английский

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Enzymes involved in metabolism of extracellular nucleotides and nucleosides: Functional implications and measurement of activities

Critical Reviews in Biochemistry and Molecular Biology, Год журнала: 2014, Номер 49(6), С. 473 - 497

Опубликована: Ноя. 1, 2014

Extracellular nucleotides and nucleosides mediate diverse signaling effects in virtually all organs tissues. Most models of purinergic depend on functional interactions between distinct processes, including (i) the release endogenous ATP other nucleotides, (ii) triggering events via a series nucleotide-selective ligand-gated P2X metabotropic P2Y receptors as well adenosine (iii) ectoenzymatic interconversion agonists. The duration magnitude is governed by network ectoenzymes, enzymes nucleoside triphosphate diphosphohydrolase (NTPDase) family, nucleotide pyrophosphatase/phosphodiesterase (NPP) ecto-5′-nucleotidase/CD73, tissue-nonspecific alkaline phosphatase (TNAP), prostatic acid (PAP) phosphatases, deaminase (ADA) purine phosphorylase (PNP). Along with "classical" inactivating recent data provide evidence for co-existence counteracting ATP-regenerating pathway comprising adenylate kinase (AK) diphosphate (NDPK/NME/NM23) families synthase. This review describes advances this field, special emphasis purine-converting ectoenzymes complex integrated regulating such (patho)physiological states immunomodulation, inflammation, tumorigenesis, arterial calcification diseases. second part provides comprehensive overview basic principles major approaches employed studying activities, spectrophotometric Pi-liberating assays, high-performance liquid chromatographic (HPLC) thin-layer (TLC) analyses substrates metabolites, capillary electrophoresis, bioluminescent, fluorometric electrochemical enzyme-coupled histochemical staining, further emphasizes their advantages, drawbacks suitability assaying particular catalytic reaction.

Язык: Английский

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Vesicular and conductive mechanisms of nucleotide release

Purinergic Signalling, Год журнала: 2012, Номер 8(3), С. 359 - 373

Опубликована: Апрель 12, 2012

Язык: Английский

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ATP Inhibits the Generation and Function of Regulatory T Cells Through the Activation of Purinergic P2X Receptors

Science Signaling, Год журнала: 2011, Номер 4(162)

Опубликована: Март 1, 2011

Extracellular nucleotides are pleiotropic regulators of mammalian cell function. Adenosine triphosphate (ATP) released from CD4(+) helper T cells upon stimulation the receptor (TCR) contributes in an autocrine manner to activation mitogen-activated protein kinase (MAPK) signaling through purinergic P2X receptors. Increased expression p2rx7, which encodes P2X7, is part transcriptional signature immunosuppressive CD4(+)CD25(+) regulatory (T(regs)). Here, we show that P2X7 by ATP inhibits suppressive potential and stability T(regs). The inflammatory cytokine interleukin-6 (IL-6) increased synthesis P2X7-mediated T(regs), induced their conversion IL-17-secreting 17 (T(H)17) effector vivo. Moreover, pharmacological antagonism receptors promoted cell-autonomous naïve into T(regs) after TCR stimulation. Thus, acts as factor integrates stimuli microenvironment cellular energetics tune developmental program adaptive immune responses.

Язык: Английский

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The role of transcription-independent damage signals in the initiation of epithelial wound healing

Nature Reviews Molecular Cell Biology, Год журнала: 2013, Номер 14(4), С. 249 - 262

Опубликована: Фев. 27, 2013

Язык: Английский

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Concepts of tissue injury and cell death in inflammation: a historical perspective

Nature reviews. Immunology, Год журнала: 2013, Номер 14(1), С. 51 - 59

Опубликована: Дек. 13, 2013

Язык: Английский

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Glucocorticoids Sensitize the Innate Immune System through Regulation of the NLRP3 Inflammasome

Journal of Biological Chemistry, Год журнала: 2011, Номер 286(44), С. 38703 - 38713

Опубликована: Сен. 23, 2011

Glucocorticoids have long been recognized as powerful anti-inflammatory compounds that are one of the most widely prescribed classes drugs in world. However, their role regulation innate immunity is not well understood. We sought to examine effects glucocorticoids on NOD-like receptors (NLRs), a central component inflammasome and immunity. Surprisingly, we show induce both NLRP3 messenger RNA protein, which critical inflammasome. The glucocorticoid-dependent induction sensitizes cells extracellular ATP significantly enhances ATP-mediated release proinflammatory molecules, including mature IL-1β, TNF-α, IL-6. This effect was specific for dependent glucocorticoid receptor. These studies demonstrate novel sensitizing initial inflammatory response by immune system.

Язык: Английский

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NAMPT and NAPRT: Two Metabolic Enzymes With Key Roles in Inflammation

Frontiers in Oncology, Год журнала: 2020, Номер 10

Опубликована: Март 19, 2020

Nicotinamide phosphoribosyltransferase (NAMPT) and nicotinate (NAPRT) are two intracellular enzymes that catalyze the first step in biosynthesis of NAD from nicotinamide nicotinic acid, respectively. By fine tuning levels, they involved regulation/reprogramming cellular metabolism control activity NAD-dependent enzymes, including sirtuins, PARPs NADases. However, during evolution both acquired novel functions as extracellular endogenous mediators inflammation. It is well known stress and/or damage induce release milieu molecules, called alarmins or damage-associated molecular patterns (DAMPs), which modulate immune through binding pattern recognition receptors (PRRs), such Toll-like (TLRs), activate inflammatory responses. Increasing evidence suggests (e)NAMPT eNAPRT soluble factors with cytokine/adipokine/DAMP-like actions. Elevated eNAMPT were reported several metabolic disorders, obesity, diabetes cancer, while emerging a biomarker sepsis septic shock. This review will discuss available data concerning dual role this unique family enzymes.

Язык: Английский

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ATP and Adenosine Metabolism in Cancer: Exploitation for Therapeutic Gain

Pharmacological Reviews, Год журнала: 2022, Номер 74(3), С. 799 - 824

Опубликована: Июнь 23, 2022

Adenosine is an evolutionary ancient metabolic regulator linking energy state to physiologic processes, including immunomodulation and cell proliferation. Tumors create adenosine-rich immunosuppressive microenvironment through the increased release of ATP from dying stressed cells its ectoenzymatic conversion into adenosine. Therefore, adenosine pathway becomes important therapeutic target improve effectiveness immune therapies. Prior research has focused largely on two major ectonucleotidases, ectonucleoside triphosphate diphosphohydrolase 1/cluster differentiation (CD)39 ecto-5′-nucleotidase/CD73, which catalyze breakdown extracellular adenosine, subsequent activation different subtypes receptors with mixed findings antitumor protumor effects. New findings, needed for more effective approaches, require consideration redundant pathways controlling intratumoral levels, alternative NAD-inactivating CD38-ectonucleotide pyrophosphatase phosphodiesterase (ENPP)1-CD73 axis, counteracting ATP-regenerating pathway, cellular uptake phosphorylation by kinase. This review provides a holistic view intracellular metabolism as integrated complex network summarizes recent data underlying mechanisms precursors ADP control cancer immunosurveillance, tumor angiogenesis, lymphangiogenesis, cancer-associated thrombosis, blood flow, perfusion. Special attention given differences commonalities in purinome cancers, heterogeneity microenvironment, subcellular compartmentalization system, novel roles purine-converting enzymes targets therapy.

Significance Statement

The discovery role checkpoint led development strategies targeting signaling multiple clinical trials preclinical models. Here we identify gaps knowledge that need be filled gain agents key components and, this basis, provide network.

Язык: Английский

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