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-Fas(lpr)) 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-Fas(lpr) 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.