title: Down-regulation of the A3 adenosine receptor in human mast cells upregulates mediators of angiogenesis and remodeling.
abstract: Adenosine activated mast cells have been long implicated in allergic asthma and studies in rodent mast cells have assigned the A3 adenosine receptor (A3R) a primary role in mediating adenosine responses. Here we analyzed the functional impact of A3R activation on genes that are implicated in tissue remodeling in severe asthma in the human mast cell line HMC-1 that shares similarities with lung derived human mast cells. Quantitative real time PCR demonstrated upregulation of IL6, IL8, VEGF, amphiregulin and osteopontin. Moreover, further upregulation of these genes was noted upon the addition of dexamethasone. Unexpectedly, activated A3R down regulated its own expression and knockdown of the receptor replicated the pattern of agonist induced gene upregulation. This study therefore identifies the human mast cell A3R as regulator of tissue remodeling gene expression in human mast cells and demonstrates a heretofore-unrecognized mode of feedback regulation that is exerted by this receptor.
authors.affiliation: Department of Cell and Developmental Biology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel.
authors.forename: Noam
authors.initials: N
authors.lastname: Rudich
authors.affiliation: Department of Cell and Developmental Biology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel.
authors.forename: Ornit
authors.initials: O
authors.lastname: Dekel
authors.affiliation: Department of Cell and Developmental Biology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel. Electronic address: histol3@post.tau.ac.il.
authors.forename: Ronit
authors.initials: R
authors.lastname: Sagi-Eisenberg
mesh_terms: D000241:Adenosine / Q000378:metabolism; D058918:Adenosine A3 Receptor Antagonists / Q000494:pharmacology; D066258:Amphiregulin; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D001249:Asthma / Q000473:pathology*; D045744:Cell Line, Tumor; D003907:Dexamethasone / Q000494:pharmacology; D015536:Down-Regulation; D066255:EGF Family of Proteins / Q000096:biosynthesis; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis; D016209:Interleukin-8 / Q000096:biosynthesis; D019169:Jurkat Cells; D008168:Lung / Q000473:pathology*; D008407:Mast Cells / Q000473:pathology*; D009389:Neovascularization, Pathologic / Q000473:pathology*; D053495:Osteopontin / Q000096:biosynthesis; D010766:Phosphorylation; D034622:RNA Interference; D034741:RNA, Small Interfering; D043684:Receptor, Adenosine A3 / Q000096:biosynthesis* / Q000235:genetics; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis
chemical_list: C587848:AREG protein, human; D058918:Adenosine A3 Receptor Antagonists; D066258:Amphiregulin; D000893:Anti-Inflammatory Agents; C508606:CXCL8 protein, human; D066255:EGF Family of Proteins; C508600:IL6 protein, human; D015850:Interleukin-6; D016209:Interleukin-8; D034741:RNA, Small Interfering; D043684:Receptor, Adenosine A3; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D053495:Osteopontin; D003907:Dexamethasone; D000241:Adenosine
keywords: A3 adenosine receptor; Adenosine; HMC-1 cells; Mast cells; Tissue remodeling