Green tea polyphenols reduce autoimmune symptoms in a murine model for human Sjogren's syndrome and protect human salivary acinar cells from TNF-α-induced cytotoxicity

Abstract

Sjogren's syndrome (SS) is a relatively common autoimmune disorder. A key feature of SS is lymphocytic infiltration of the salivary and lacrimal glands, associated with the destruction of secretory functions of these glands. Current treatment of SS targets the symptoms but is unable to reduce or prevent the damage to the glands. We reported previously that the major green tea polyphenol (GTP) epigallocatechin-3-gallate (EGCG) inhibits autoantigen expression in normal human keratinocytes and immortalized normal human salivary acinar cells (Hsu et al. 2005). However, it is not known whether GTPs have this effect in vivo, if they can reduce lymphocytic infiltration, or protect salivary acinar cells from tumor necrosis factor-α (TNF-α)-induced cytotoxicity. Here, we demonstrate that in the NOD mouse, a model for human SS, oral administration of green tea extract reduced the serum total autoantibody levels and the autoimmune-induced lymphocytic infiltration of the submandibular glands. Further, we show that EGCG protected normal human salivary acinar cells from TNF-α-induced cytotoxicity. This protection was associated with specific phosphorylation of p38 MAPK, and inhibitors of the p38 MAPK pathway blocked the protective effect. In conclusion, GTPs may provide a degree of protection against autoimmune-induced tissue damage in SS, mediated in part through activation of MAPK elements.

• Green tea polyphenols
• EGCG
• Sjogren's syndrome
• acinar cells
• MAPK

Acknowledgements

The authors thank Dr Robert Podolsky for statistical assistance and Laura McKie for graphical work. This study was supported in part by funds from NIH grant CA097258-01A1, and Department of Oral Biology and Maxillofacial Pathology, School of Dentistry to S.H.

Notes

^*This study was supported in part by funds from NIH grant CA097258, and Department of Oral Biology and Maxillofacial Pathology, School of Dentistry to S.H. Data in this manuscript was presented in poster form at the annual meeting of the American Association for Dental Research, 2006.