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

Youngmi Kim, Sangkyung Eom, Kyungjong Kim, Yun Sil Lee, Jongseon Choe, Jang Hee Hahn, Hansoo Lee, Young Myeong Kim, Kwon Soo Ha, Jai Youl Ro, Dooil Jeoung

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39 Scopus citations

Abstract

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-κB in rat basophilic leukemia (RBL2H3) cells. This induction of TGase II was dependent on FcεRI 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-κB, 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.

Original languageEnglish
Pages (from-to)1010-1022
Number of pages13
JournalMolecular Immunology
Volume47
Issue number5
DOIs
StatePublished - Feb 2010

Bibliographical note

Funding Information:
This work was supported by a grant from the Korea Research Foundation (C1001478-01-01, C1006272-01-01 and C1006625-01-01), Vascular Research Center, a grant from (A050260) from the Ministry of Health and Welfare of Korea, a grant (FG06-2-23) from the 21C Frontier Functional Human Genome Project from the Ministry of Science & Technology in Korea. This work was also supported by the Regional Innovation Center Program of the Ministry of Commerce, Industry, and Energy. This work was also supported by a grant from Korea Research Foundation Grant funded by the Korean Government (MEST) (The Regional Research Universities Program/Medical & Bio-Materials Research Center).

Keywords

  • Allergic inflammation
  • Histone deacetylase 3
  • Reactive oxygen species
  • Snail
  • Transglutaminase II

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