title: Transglutaminase II/microRNA-218/-181a loop regulates positive feedback relationship between allergic inflammation and tumor metastasis.
abstract: The molecular mechanism of transglutaminase II (TGaseII)-mediated allergic inflammation remains largely unknown. TGaseII, induced by antigen stimulation, showed an interaction and co-localization with FcϵRI. TGaseII was necessary for in vivo allergic inflammation, such as triphasic cutaneous reaction, passive cutaneous anaphylaxis, and passive systemic anaphylaxis. TGaseII was necessary for the enhanced metastatic potential of B16F1 melanoma cells by passive systemic anaphylaxis. TGaseII was shown to be a secreted protein. Recombinant TGaseII protein increased the histamine release and β-hexosaminidase activity, and enhanced the metastatic potential of B16F1 mouse melanoma cells. Recombinant TGaseII protein induced the activation of EGF receptor and an interaction between EGF receptor and FcϵRI. Recombinant TGaseII protein displayed angiogenic potential accompanied by allergic inflammation. R2 peptide, an inhibitor of TGaseII, exerted negative effects on in vitro and in vivo allergic inflammation by regulating the expression of TGaseII and FcϵRI signaling. MicroRNA (miR)-218 and miR-181a, decreased during allergic inflammation, were predicted as negative regulators of TGaseII by microRNA array and TargetScan analysis. miR-218 and miR-181a formed a negative feedback loop with TGaseII and regulated the in vitro and in vivo allergic inflammation. TGaseII was necessary for the interaction between mast cells and macrophages during allergic inflammation. Mast cells and macrophages, activated during allergic inflammation, were responsible for the enhanced metastatic potential of tumor cells that are accompanied by allergic inflammation. In conclusion, the TGaseII/miR-218/-181a feedback loop can be employed for the development of anti-allergy therapeutics.
authors.affiliation: From the Departments of Biochemistry and.
authors.forename: Sangkyung
authors.initials: S
authors.lastname: Eom
authors.affiliation: From the Departments of Biochemistry and.
authors.forename: Youngmi
authors.initials: Y
authors.lastname: Kim
authors.affiliation: From the Departments of Biochemistry and.
authors.forename: Misun
authors.initials: M
authors.lastname: Kim
authors.affiliation: From the Departments of Biochemistry and.
authors.forename: Deokbum
authors.initials: D
authors.lastname: Park
authors.affiliation: Biological Sciences, College of Natural Sciences, and.
authors.forename: Hansoo
authors.initials: H
authors.lastname: Lee
authors.affiliation: the College of Pharmacy, Ewha Womans University, Seoul 120-750, Korea.
authors.forename: Yun Sil
authors.initials: YS
authors.lastname: Lee
authors.affiliation: Graduate School of Medicine, Kangwon National University, Chunchon 200-701, Korea, and.
authors.forename: Jongseon
authors.initials: J
authors.lastname: Choe
authors.affiliation: Graduate School of Medicine, Kangwon National University, Chunchon 200-701, Korea, and.
authors.forename: Young Myeong
authors.initials: YM
authors.lastname: Kim
authors.affiliation: From the Departments of Biochemistry and jeoungd@kangwon.ac.kr.
authors.forename: Dooil
authors.initials: D
authors.lastname: Jeoung
mesh_terms: D000818:Animals; D000941:Antigens / Q000378:metabolism; D001483:Base Sequence; D002465:Cell Movement / Q000187:drug effects; D066246:ErbB Receptors / Q000378:metabolism; D025461:Feedback, Physiological / Q000187:drug effects; D005260:Female; D019204:GTP-Binding Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006967:Hypersensitivity / Q000150:complications / Q000235:genetics / Q000473:pathology*; D007249:Inflammation / Q000150:complications / Q000235:genetics / Q000473:pathology*; D008262:Macrophage Activation / Q000187:drug effects; D008297:Male; D008407:Mast Cells / Q000187:drug effects / Q000378:metabolism; D008545:Melanoma / Q000098:blood supply / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D035683:MicroRNAs / Q000378:metabolism*; D008969:Molecular Sequence Data; D009362:Neoplasm Metastasis; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000473:pathology; D010323:Passive Cutaneous Anaphylaxis / Q000235:genetics; D010455:Peptides / Q000494:pharmacology; D011485:Protein Binding / Q000187:drug effects; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D017455:Receptors, IgE / Q000378:metabolism; D012867:Skin / Q000473:pathology; D011503:Transglutaminases / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D000941:Antigens; C521907:Fc-epsilon receptor I beta-chain, mouse; C547684:MIRN218 microRNA, mouse; D035683:MicroRNAs; D010455:Peptides; D017455:Receptors, IgE; C529100:mirn181 microRNA, mouse; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D066246:ErbB Receptors; D019204:GTP-Binding Proteins
keywords: Allergic Inflammation; Angiogenesis; Gene Regulation; Macrophage; Mast Cell; MicroRNA-181a; MicroRNA-218; Transglutaminase II; Tumor Metastasis