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

Autoimmunity. 2007 Mar;40(2):138-47. doi: 10.1080/08916930601167343.


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-alpha (TNF-alpha)-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-alpha-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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autoimmunity*
  • Catechin / analogs & derivatives
  • Catechin / pharmacology
  • Cell Line
  • Cell Survival / drug effects
  • Disease Models, Animal
  • Flavonoids / pharmacology*
  • Humans
  • Imidazoles / pharmacology
  • Lymphocytes / immunology
  • Lymphocytes / pathology
  • MAP Kinase Kinase 4 / metabolism
  • MAP Kinase Kinase Kinases / antagonists & inhibitors
  • Mice
  • Mice, Inbred NOD
  • Phenols / pharmacology*
  • Phosphorylation
  • Plant Extracts / pharmacology*
  • Polyphenols
  • Pyridines / pharmacology
  • Salivary Glands / drug effects*
  • Salivary Glands / pathology
  • Sjogren's Syndrome / immunology*
  • Sjogren's Syndrome / pathology
  • Tea / chemistry*
  • Tumor Necrosis Factor-alpha / pharmacology
  • Tumor Necrosis Factor-alpha / physiology*
  • p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors


  • Flavonoids
  • Imidazoles
  • Phenols
  • Plant Extracts
  • Polyphenols
  • Pyridines
  • Tea
  • Tumor Necrosis Factor-alpha
  • Catechin
  • epigallocatechin gallate
  • p38 Mitogen-Activated Protein Kinases
  • MAP Kinase Kinase Kinases
  • MAP Kinase Kinase 4
  • SB 203580
  • 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one