DNA methyl transferase I acts as a negative regulator of allergic skin inflammation

Youngmi Kim, Kyungjong Kim, Deokbum Park, Eunmi Lee, Hansoo Lee, Yun Sil Lee, Jongseon Choe, Young Myeong Kim, Dooil Jeoung

Research output: Contribution to journalArticlepeer-review

18 Scopus citations


The role of DNA methyl transferase I (DNMT1) in allergic inflammation was investigated. Antigen stimulation decreased expression of DNMT1 in rat basophilic leukemia cells (RBL2H3). The down regulation of DNMT1 induced expression of histone deacetylase 3 (HDAC3). HDAC3 was necessary for allergic skin inflammation, such as such as triphasic cutaneous reaction and passive cutaneous anaphylaxis. The down regulation of DNMT1 resulted from activation of PKC and rac1 which were necessary for proteasome-dependent ubiquitination of DNMT1 by antigen stimulation. N-acetyl-L-cysteine, an inhibitor of reactive oxygen species production, exerted negative effects on allergic skin inflammation. Antigen stimulation led to increased expression of Tip60, a histone acetyl transferase. Wild type, but not mutant form, Tip60 decreased expression of DNMT1 while increasing expression of HDAC3, suggesting role for acetylation in ubiquitin-dependent proteasomal degradation of DNMT1. In vivo down regulation of DNMT1 increased ear thickness, typical of allergic skin inflammation, induced vascular leakage and promoted angiogenesis in BALB/c mouse. The down regulation of DNMT1 enhanced angiogenic potential of rat aortic endothelial cells (RAEC) accompanied by activation of VEGR-2 and induced interaction between VEGR-2 and syk in RAEC. The enhanced angiogenic potential of RAEC was associated with the induction of VEGF by down regulation of DNMT1 in RBL2H3 cells. The down regulation of DNMT1 induced leukocytes-endothelial cell interaction and expression of various adhesion molecules. Aspirin exerted a negative effect on allergic skin inflammation by indirect regulation on DNMT1 via Tip60. Taken together, these results suggest novel role for DNMT1 in allergic skin inflammation.

Original languageEnglish
Pages (from-to)1-14
Number of pages14
JournalMolecular Immunology
Issue number1-2
StatePublished - Jan 2013

Bibliographical note

Funding Information:
This work was supported by a grant from the Korea Research Foundation ( 2011-0003890 , 2011-0011867 and 2010-0021357 ), a grant from the Regional Innovation Center Program of the Ministry of Education, Science and Technology . 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).


  • Allergic inflammation
  • Angiogenesis
  • DNMT1
  • HDAC3


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