Epigallocatechin gallate inhibits oxidative stress-induced DNA damage and apoptosis in MRL-Faslpr mice with autoimmune sialadenitis via upregulation of heme oxygenase-1 and Bcl-2

Keiichi Saito, Shiro Mori, Fumiko Date, Masao Ono

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Pathogenic effects of reactive oxygen species (ROS) in the salivary glands of patients with Sjögren's syndrome have been demonstrated. Epigallocatechin gallate (EGCG), which is a catechin derivative and exhibits potent antioxidant activity, has been reported to ameliorate autoimmune sialadenitis in a murine model, but the mechanism underlying its protective action remains to be investigated. Herein, we examined the effects of EGCG administration to MRL/MpJ-lpr/lpr (MRL-Faslpr) mice on disease severity of autoimmune sialadenitis and protein expression levels of 11 sialadenitis-related molecules-heme oxygenase-1 (HO-1) (antioxidant); thymidine glycol (marker of DNA damage); gp91phox/NADPH oxidase 2 (prooxidant); single-stranded DNA (ssDNA) and cleaved caspase 3 (apoptotic cell markers); p53 and Bax (proapoptotic molecules); Bcl-2 (antiapoptotic molecule); SSA/Ro, SSB/La, and Ifi202 (autoantigens). In EGCG-treated mice, the severity of sialadenitis was substantially decreased. Expression levels of thymidine glycol, gp91phox, ssDNA, cleaved caspase 3, p53, Bax, SSA/Ro, SSB/La, and Ifi202 in duct epithelial cells of salivary glands from EGCG-treated mice were reduced, whereas HO-1 and Bcl-2 were overexpressed. Results of correlation analysis among sialadenitis severity and 11 sialadenitis related-molecules, and those of partial correlation analysis between apoptotic related-molecules and sialadenitis severity or HO-1 suggested that the consecutive pathogenic cycle including activated autoimmune reactions, ROS synthesis, DNA damage and p53-dependent apoptosis was associated with the pathogenesis of autoimmune sialadenitis in MRL-Faslpr mice. Overexpression of HO-1 and Bcl-2 mediated by EGCG blocked this pathogenic cycle, subsequently resulting in the inhibition of ROS-mediated DNA damage and apoptosis, and protected salivary gland tissues from oxidative stress. Clinically, green tea catechin may have therapeutic efficacy for Sjögren's syndrome.

Original languageEnglish
Pages (from-to)13-22
Number of pages10
JournalAutoimmunity
Volume47
Issue number1
DOIs
Publication statusPublished - 2014 Feb 1

Keywords

  • Antioxidant
  • Gp91phox/Nox2
  • Green tea catechin
  • Ifi202
  • Reactive oxygen species
  • Sjögren's syndrome
  • SsDNA
  • Thymidine glycol

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Fingerprint Dive into the research topics of 'Epigallocatechin gallate inhibits oxidative stress-induced DNA damage and apoptosis in MRL-Fas<sup>lpr</sup> mice with autoimmune sialadenitis via upregulation of heme oxygenase-1 and Bcl-2'. Together they form a unique fingerprint.

  • Cite this