Nucleoside 5’- O -monophosphorothioates as modulators of the P2Y14 receptor and mast cell degranulation

Edyta Gendaszewska-Darmach; Edyta Węgłowska; Aurelia Walczak-Drzewiecka; Kaja Karaś

doi:10.18632/oncotarget.12541

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Research Papers: Immunology:

Nucleoside 5’-O-monophosphorothioates as modulators of the P2Y14 receptor and mast cell degranulation

Edyta Gendaszewska-Darmach _, Edyta Węgłowska, Aurelia Walczak-Drzewiecka and Kaja Karaś

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Oncotarget. 2016; 7:69358-69370. https://doi.org/10.18632/oncotarget.12541

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Abstract

Edyta Gendaszewska-Darmach1, Edyta Węgłowska1, Aurelia Walczak-Drzewiecka2 and Kaja Karaś1

1 Institute of Technical Biochemistry, Faculty of Biotechnology and Food Sciences, Lodz University of Technology, Stefanowskiego, Lodz, Poland

2 Laboratory of Cellular Immunology, Institute of Medical Biology, Polish Academy of Sciences, Lodowa, Lodz, Poland

Correspondence to:

Edyta Gendaszewska-Darmach, email:

Keywords: P2Y receptors, nucleoside 5’-O-monophosphorothioates, inflammation, degranulation, RBL-2H3 cells, Immunology and Microbiology Section, Immune response, Immunity

Received: May 12, 2016 Accepted: September 24, 2016 Published: October 09, 2016

Abstract

Mast cells (MCs) are long-lived resident cells known for their substantial role in antigen-induced anaphylaxis and other immunoglobulin E-mediated allergic reactions as well as tumor promotion. MCs’ activation results in the release of pro-inflammatory factors such as histamine, tryptase, tumor necrosis factor or carboxypeptidase A stored in secretory granules. IgE-dependent hypersensitivity has been thought to be the major pathway mediating degranulation of mast cells, but the P2Y14 nucleotide receptor activated by UDP-glucose (UDPG) may also enhance this process. In this study we identified thymidine 5’-O-monophosphorothioate (TMPS) as a molecule inhibiting UDPG-induced degranulation in a rat mast cell line (RBL-2H3). Additionally, TMPS diminished UDPG-evoked intracellular calcium mobilization in a stable HEK293T cell line overexpressing the P2Y14 receptor. Therefore, we demonstrate that the use of thymidine 5’-O-monophosphorothioate might be a novel anti-inflammatory approach based on preventingmast cell activation.

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Research Papers: Immunology:

Nucleoside 5’-O-monophosphorothioates as modulators of the P2Y14 receptor and mast cell degranulation

Abstract