UDP-glucose promotes neutrophil recruitment in the lung

Sesma, Juliana I.; Weitzer, Clarissa D.; Livraghi‐Butrico, Alessandra; Dang, Hong; Donaldson, Scott H.; Alexis, Neil E.; Jacobson, Kenneth A.; Harden, T. Kendall; Lazarowski, Eduardo R.

doi:10.1007/s11302-016-9524-5

Cited by 50 publications

(78 citation statements)

References 55 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…inconsistence. It is known that UDPG could be released from Golgi to the extracellular space through a secretory pathway 30,31 , where UDPG bound to the receptor P2Y 14 for signal transduction [18][19][20]31,32 . Notably, the expression of P2Y 14 receptor was upregulated in IFN-γ/LPS-treated macrophages (Fig.…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Glycogen metabolism regulates macrophage-mediated acute inflammatory responses

et al. 2020

View full text Add to dashboard Cite

Our current understanding of how sugar metabolism affects inflammatory pathways in macrophages is incomplete. Here, we show that glycogen metabolism is an important event that controls macrophage-mediated inflammatory responses. IFN-γ/LPS treatment stimulates macrophages to synthesize glycogen, which is then channeled through glycogenolysis to generate G6P and further through the pentose phosphate pathway to yield abundant NADPH, ensuring high levels of reduced glutathione for inflammatory macrophage survival. Meanwhile, glycogen metabolism also increases UDPG levels and the receptor P2Y 14 in macrophages. The UDPG/P2Y 14 signaling pathway not only upregulates the expression of STAT1 via activating RARβ but also promotes STAT1 phosphorylation by downregulating phosphatase TC45. Blockade of this glycogen metabolic pathway disrupts acute inflammatory responses in multiple mouse models. Glycogen metabolism also regulates inflammatory responses in patients with sepsis. These findings show that glycogen metabolism in macrophages is an important regulator and indicate strategies that might be used to treat acute inflammatory diseases.

show abstract

Section: Resultsmentioning

confidence: 99%

“…These findings imply that glycogen may exert important biological effects through metabolic pathways beyond its role as a reservoir of glucose. In support of this notion, UDPglucose (UDPG), a glycogen metabolic intermediate, has been shown to act as a ligand for purigenic receptor P2Y 14 , thus directly triggering signal transduction [18][19][20] .…”

mentioning

confidence: 98%

Glycogen metabolism regulates macrophage-mediated acute inflammatory responses

et al. 2020

View full text Add to dashboard Cite

show abstract

“…P2Y 14 receptors activation promotes chemotaxis in human neutrophils, as studied in cystic fibrosis (Sesma et al, 2016), the release of proinflammatory cytokines from renal intercalated cells in sterile inflammation (Azroyan et al, 2015), and the degranulation of mast cells (Gao, Wei, Jayasekara, & Jacobson, 2013). Thus, P2Y 14 receptor antagonists are being developed for anti‐inflammatory applications (Junker et al, 2016).…”

Section: P2y Receptors In Immune and Pulmonary Functionmentioning

confidence: 99%

Update of P2Y receptor pharmacology: IUPHAR Review 27

Jacobson

Delicado

Gachet

et al. 2020

British J Pharmacology

Self Cite

170

184

View full text Add to dashboard Cite

Eight G protein-coupled P2Y receptor subtypes respond to extracellular adenine and uracil mononucleotides and dinucleotides. P2Y receptors belong to the δ group of rhodopsin-like GPCRs and contain two structurally distinct subfamilies: P2Y 1 , P2Y 2 , P2Y 4 , P2Y 6 , and P2Y 11 (principally G q protein-coupled P2Y 1 -like) and P2Y 12-14 (principally G i protein-coupled P2Y 12 -like) receptors. Brain P2Y receptors occur in neurons, glial cells, and vasculature. Endothelial P2Y 1 , P2Y 2 , P2Y 4 , and P2Y 6 receptors induce vasodilation, while smooth muscle P2Y 2 , P2Y 4 , and P2Y 6 receptor activation leads to vasoconstriction. Pancreatic P2Y 1 and P2Y 6 receptors stimulate while P2Y 13 receptors inhibits insulin secretion. Antagonists of P2Y 12 receptors, and potentially P2Y 1 receptors, are anti-thrombotic agents, and a P2Y 2 /P2Y 4 receptor agonist treats dry eye syndrome in Asia. P2Y receptor agonists are generally pro-inflammatory, and antagonists may eventually treat inflammatory conditions. This article reviews recent developments in P2Y receptor pharmacology (using synthetic agonists and antagonists), structure and biophysical properties (using X-ray crystallography, mutagenesis and modelling), physiological and pathophysiological roles, and present and potentially future therapeutic targeting.Abbreviations: BMD, bone mineral density; DUSP, dual specificity protein phosphatase; ECL, extracellular loop; EPAC, exchange protein activated by cAMP; KO, knockout; MSD, musculoskeletal disorder; SNP, single nucleotide polymorphism; SS, Sjögren's syndrome; TM, transmembrane helix.

show abstract

“…This receptor subtype is expressed by leukocytes, thus pointing out a possible effect in inflammation [246]. It has been shown that the activation of P2Y 14 Rs promoted the chemotaxis of neutrophils [247,248], specifically in the lungs [249]. and maturation [133].…”

Section: P2y 14mentioning

confidence: 99%

Tackling Chronic Pain and Inflammation through the Purinergic System

Magni

Riccio

Ceruti

2018

CMC

View full text Add to dashboard Cite

The purinergic system is composed of purine and pyrimidine transmitters, of the enzymes that modulate the interconversion of nucleotides and nucleosides, of the membrane transporters that control their extracellular concentrations, and of the many receptor subtypes that are responsible for their cellular responses. The components of this system are ubiquitously localized in all tissues and organs, and their involvement in several physiological conditions has been clearly demonstrated. Moreover, extracellular purine and pyrimidine concentrations raise several folds under pathological conditions like tissue damage, ischemia, and inflammation, which suggest that this signaling system might contribute both to disease outcome and, possibly, to its tentative resolution. The complexity of this system has greatly impaired the clear identification of the mediators and receptors that are actually involved in a given pathology, also due to the often opposite roles played by the various receptor subtypes. Nevertheless, this knowledge is fundamental for the possible exploitation of these molecular entities as targets for the development of new pharmacological approaches. In this review, we aim at highlighting what is currently known on the role of the purinergic system in various pain conditions and during inflammatory processes. Although some confusion may arise from conflicting 2 results, literature data clearly show that targeting specific purinergic receptors may represent an innovative approach to various pain and inflammatory conditions, and that new purine-based drugs are now very close to reach the market with these indications.

show abstract

UDP-glucose promotes neutrophil recruitment in the lung

Cited by 50 publications

References 55 publications

Glycogen metabolism regulates macrophage-mediated acute inflammatory responses

Glycogen metabolism regulates macrophage-mediated acute inflammatory responses

Update of P2Y receptor pharmacology: IUPHAR Review 27

Tackling Chronic Pain and Inflammation through the Purinergic System

Contact Info

Product

Resources

About