Inhibition of Autoantigen Expression by (-)-Epigallocatechin-3-gallate (the Major Constituent of Green Tea) in Normal Human Cells

Hsu, Stephen; Dickinson, Douglas; Qin, Haiyan; Lapp, Carol A.; Lapp, David; Borke, James L.; Walsh, Douglas S.; Bollag, Wendy B.; Stöppler, Hubert; Yamamoto, Tetsuya; Osaki, Tokio; Schuster, George S.

doi:10.1124/jpet.105.090399

Cited by 23 publications

(16 citation statements)

References 35 publications

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“…We found previously that GTPs or EGCG, at a topically achievable range, selectively induced caspase 3-dependent apoptosis in tumor cells, while normal human epidermal keratinocytes (NHEK) showed elevated expression of p57 ⁄ KIP2 and underwent terminal differentiation in response to EGCG, without activation of caspase 3 (20)(21)(22)(23). Results from our recent study demonstrated an inhibitory effect of EGCG on autoantigen expression, and are consistent with a green tea-activated differentiation pathway (24,25).…”

Section: Introductionsupporting

confidence: 85%

Green tea polyphenol induces caspase 14 in epidermal keratinocytes via MAPK pathways and reduces psoriasiform lesions in the flaky skin mouse model

Hsu

Dickinson

Borke

et al. 2007

Experimental Dermatology

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Psoriasiform lesions are characterized by hyperproliferation and aberrant differentiation of epidermal keratinocytes, accompanied by inflammation, leading to a disrupted skin barrier with an abnormal stratum corneum. The expression and proteolytic processing of caspase 14, a member of the caspase family which is associated with epithelial cell differentiation, planned cell death, and barrier formation, is altered in psoriatic epidermis. We recently reported that human psoriatic tissues lack normal expression of caspase 14 [J Dermatol Sci37 (2005) 61], and caspase 14 is induced by EGCG, a green tea polyphenol (GTP), in exponentially growing normal human epidermal keratinocytes (NHEK) [J Pharmacol Exp Ther315 (2005) 805]. This suggests that GTPs may have beneficial effects on psoriasiform lesions. The current study aimed to determine whether MAPK pathways are required for GTP-induced caspase 14 expression in NHEK and if GTPs can modulate the expression of pathological markers in the psoriasiform lesions that develop in the flaky skin mouse. The results indicate that the p38 and JNK MAPK pathways are required for EGCG-induced expression of caspase 14 in NHEK. Importantly, topical application of 0.5% GTPs significantly reduced the symptoms of epidermal pathology in the flaky skin mice, associated with efficient caspase 14 processing and reduction in proliferating cell nuclear antigen levels. This suggests that GTP-activated pathways may be potential targets for novel therapeutic approaches to the treatment of some psoriasiform skin disorders.

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Section: Introductionsupporting

confidence: 85%

Green tea polyphenol induces caspase 14 in epidermal keratinocytes via MAPK pathways and reduces psoriasiform lesions in the flaky skin mouse model

Hsu

Dickinson

Borke

et al. 2007

Experimental Dermatology

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“…A previous in vitro study using normal human salivary acinar cells showed that EGCG abrogated the expression of autoantigens SSA and SSB at the mRNA and protein level [74]. In our in vivo study, we also showed that EGCG blocked the expression of SSA, SSB, and Ifi202 in autoimmune sialadenitis lesions.…”

Section: Discussionsupporting

confidence: 71%

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

et al. 2014

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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.

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“…On the other hand, inhibition of cell proliferation by EGCG might be achieved by its pro-differentiation property previously described (Hsu et al, 2003). Finally, the relatively low levels of serum total autoantibodies could be resulted from EGCG’s inhibitory effect on autoantigen expression (Hsu et al, 2005). …”

Section: Discussionmentioning

confidence: 99%

Effects of oral consumption of the green tea polyphenol EGCG in a murine model for human Sjogren's syndrome, an autoimmune disease

Gillespie¹,

Kodani

Dickinson

et al. 2008

Life Sciences

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Protection of glandular acinar cells from autoimmune-induced damage would be of significant clinical benefit to Sjogren's syndrome (SS) patients. EGCG (the most abundant green tea polyphenol) possesses anti-apoptotic, anti-inflammatory, and autoantigen-inhibitory properties. To investigate if EGCG can protect against certain autoimmune-induced pathological changes in the salivary glands of the non-obese diabetic (NOD) mouse model for SS-like symptoms, animals were provided with either water or water containing 0.2% EGCG. At the age of 8, 16 and 22 weeks, samples were collected for pathological and serological analysis. Massive lymphocyte infiltration was observed in the salivary glands of the water-fed group at the age of 16 weeks, while the EGCG group showed significantly reduced lymphocyte infiltration. By 22 weeks of age, animals fed with water demonstrated elevated levels of apoptotic activity within the lymphocytic infiltrates, and high levels of serum total anti-nuclear antibody, in comparison with the animals fed with EGCG. Remarkably, proliferating cell nuclear antigen (PCNA) and Ki-67 levels in the salivary glands of NOD animals fed with water were significantly elevated in comparison to BALB/c control mice; in contrast, PCNA and Ki-67 levels in EGCG-fed NOD animals were similar to BALB/c controls. These results indicate that EGCG is able to protect the NOD mouse submandibular glands from autoimmune-induced inflammation, and reduces serum autoantibody levels. Abnormal proliferation, rather than apoptosis, appears to be a characteristic of the NOD mouse gland that is normalized by EGCG. The evidence suggests that EGCG could ultimately be used to delay or manage SS-like autoimmune disorders.

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Inhibition of Autoantigen Expression by (-)-Epigallocatechin-3-gallate (the Major Constituent of Green Tea) in Normal Human Cells

Cited by 23 publications

References 35 publications

Green tea polyphenol induces caspase 14 in epidermal keratinocytes via MAPK pathways and reduces psoriasiform lesions in the flaky skin mouse model

Green tea polyphenol induces caspase 14 in epidermal keratinocytes via MAPK pathways and reduces psoriasiform lesions in the flaky skin mouse model

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

Effects of oral consumption of the green tea polyphenol EGCG in a murine model for human Sjogren's syndrome, an autoimmune disease

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Inhibition of Autoantigen Expression by (-)-Epigallocatechin-3-gallate (the Major Constituent of Green Tea) in Normal Human Cells

Cited by 23 publications

References 35 publications

Green tea polyphenol induces caspase 14 in epidermal keratinocytes via MAPK pathways and reduces psoriasiform lesions in the flaky skin mouse model

Green tea polyphenol induces caspase 14 in epidermal keratinocytes via MAPK pathways and reduces psoriasiform lesions in the flaky skin mouse model

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

Effects of oral consumption of the green tea polyphenol EGCG in a murine model for human Sjogren's syndrome, an autoimmune disease

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Product

Resources

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