title: Nucleoside 5'-O-monophosphorothioates as modulators of the P2Y14 receptor and mast cell degranulation.
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.
authors.affiliation: Institute of Technical Biochemistry, Faculty of Biotechnology and Food Sciences, Lodz University of Technology, Stefanowskiego, Lodz, Poland.
authors.forename: Edyta
authors.initials: E
authors.lastname: Gendaszewska-Darmach
authors.affiliation: Institute of Technical Biochemistry, Faculty of Biotechnology and Food Sciences, Lodz University of Technology, Stefanowskiego, Lodz, Poland.
authors.forename: Edyta
authors.initials: E
authors.lastname: Węgłowska
authors.affiliation: Laboratory of Cellular Immunology, Institute of Medical Biology, Polish Academy of Sciences, Lodowa, Lodz, Poland.
authors.forename: Aurelia
authors.initials: A
authors.lastname: Walczak-Drzewiecka
authors.affiliation: Institute of Technical Biochemistry, Faculty of Biotechnology and Food Sciences, Lodz University of Technology, Stefanowskiego, Lodz, Poland.
authors.forename: Kaja
authors.initials: K
authors.lastname: Karaś
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D015550:Cell Degranulation / Q000187:drug effects*; D045744:Cell Line, Tumor; D057809:HEK293 Cells; D006801:Humans; D008407:Mast Cells / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D051381:Rats; D018048:Receptors, Purinergic P2 / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013873:Thionucleotides / Q000737:chemistry / Q000494:pharmacology*; D013936:Thymidine / Q000737:chemistry / Q000494:pharmacology; D014532:Uridine Diphosphate Glucose / Q000494:pharmacology; D001619:beta-N-Acetylhexosaminidases / Q000378:metabolism
chemical_list: C518528:P2Y14 receptor, human; D018048:Receptors, Purinergic P2; D013873:Thionucleotides; D001619:beta-N-Acetylhexosaminidases; D002118:Calcium; D014532:Uridine Diphosphate Glucose; D013936:Thymidine
keywords: Immune response; Immunity; Immunology and Microbiology Section; P2Y receptors; RBL-2H3 cells; degranulation; inflammation; nucleoside 5’-O-monophosphorothioates