Transglutaminase II interacts with rac1, regulates production of reactive oxygen species, expression of snail, secretion of Th2 cytokines and mediates in vitro and in vivo allergic inflammation.
Transglutaminase II (TGase II) is a protein cross-linking enzyme with diverse biological functions. Here we report the role of TGase II in allergic inflammation. Antigen stimulation induced expression and activity of TGase II by activation of NF-kappaB in rat basophilic leukemia (RBL2H3) cells. This induction of TGase II was dependent on FcepsilonRI and EGFR. Interaction between TGase II and rac1 was induced following antigen stimulation. TGase II was responsible for the increased production of reactive oxygen species, expression of prostaglandin E2 synthase (PGE2 synthase) and was responsible for increased secretion of prostaglandin E2. ChIP assay showed that TGase II, through interaction with NF-kappaB, was responsible for the induction of histone deacetylase-3 (HDAC3) and snail by direct binding to promoter sequences. HDAC3 and snail induced by TGase II, exerted transcriptional repression on E-cadherin. Snail exerted negative effect on expression of MMP-2, and secretion of Th2 cytokines. Inhibition of matrix metalloproteinase-2 (MMP-2) inhibited secretion of Th2 cytokines. In vivo induction of TGase II was observed in Balb/c mouse model of IgE antibody-induced passive cutaneous anaphylaxis. Chemical inhibition of TGase II exerted negative effect on IgE-dependent passive cutaneous anaphylaxis. Chemical inhibition of TGase II by cystamine exerted negative effect on Balb/c mouse model of phorbol myristate acetate (PMA)-induced atopic dermatitis. These results suggest novel role of TGase II in allergic inflammation and TGase II can be developed as target for the development of allergy therapeutics.
Kim
Youngmi
Y
School of Biological Sciences, College of Natural Sciences, Kangwon National University, Chunchon, Republic of Korea.
Eom
Sangkyung
S
Kim
Kyungjong
K
Lee
Yun-Sil
YS
Choe
Jongseon
J
Hahn
Jang Hee
JH
Lee
Hansoo
H
Kim
Young-Myeong
YM
Ha
Kwon Soo
KS
Ro
Jai Youl
JY
Jeoung
Dooil
D
D000707:Anaphylaxis / Q000139:chemically induced / Q000201:enzymology / Q000276:immunology*; D000818:Animals; D000941:Antigens / Q000276:immunology / Q000378:metabolism; D015820:Cadherins / Q000276:immunology / Q000378:metabolism; D002273:Carcinogens / Q000633:toxicity; D045744:Cell Line, Tumor; D016207:Cytokines / Q000276:immunology* / Q000378:metabolism; D003876:Dermatitis, Atopic / Q000139:chemically induced / Q000201:enzymology / Q000276:immunology*; D015232:Dinoprostone / Q000276:immunology / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000276:immunology* / Q000378:metabolism; D006655:Histone Deacetylases / Q000276:immunology / Q000378:metabolism; D007249:Inflammation / Q000201:enzymology / Q000276:immunology; D019746:Intramolecular Oxidoreductases / Q000276:immunology / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000276:immunology / Q000378:metabolism; D009479:Neuropeptides / Q000276:immunology* / Q000378:metabolism; D000071876:Prostaglandin-E Synthases; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D051381:Rats; D017382:Reactive Oxygen Species / Q000276:immunology* / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000633:toxicity; D018418:Th2 Cells / Q000201:enzymology / Q000276:immunology*; D014158:Transcription, Genetic; D011503:Transglutaminases / Q000276:immunology* / Q000378:metabolism; D020744:rac GTP-Binding Proteins / Q000276:immunology* / Q000378:metabolism; D020830:rac1 GTP-Binding Protein / Q000276:immunology* / Q000378:metabolism; D000099186:Histone Deacetylase 3
D000941:Antigens; D015820:Cadherins; D002273:Carcinogens; D016207:Cytokines; D015232:Dinoprostone; D019204:GTP-Binding Proteins; D006655:Histone Deacetylases; D019746:Intramolecular Oxidoreductases; D020778:Matrix Metalloproteinase 2; D016328:NF-kappa B; D009479:Neuropeptides; D000071876:Prostaglandin-E Synthases; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D017382:Reactive Oxygen Species; D013755:Tetradecanoylphorbol Acetate; D011503:Transglutaminases; D020744:rac GTP-Binding Proteins; D020830:rac1 GTP-Binding Protein; D000099186:Histone Deacetylase 3; C484602:Rac1 protein, mouse; C499134:Rac1 protein, rat