Inhibition of Autoantigen Expression by (-)-Epigallocatechin-3-gallate (the Major Constituent of Green Tea) in Normal Human Cells
- Stephen Hsu,
- Douglas P. Dickinson,
- Haiyan Qin,
- Carol Lapp,
- David Lapp,
- James Borke,
- Douglas S. Walsh,
- Wendy B. Bollag,
- Hubert Stöppler,
- Tetsuya Yamamoto,
- Tokio Osaki and
- George Schuster
- Department of Oral Biology and Maxillofacial Pathology, School of Dentistry, Medical College of Georgia, Augusta, Georgia (S.H., D.P.D., H.Q., C.L., J.B., G.S.); Department of Oral Surgery, Kochi Medical School, Kochi, Japan (T.Y., T.O.); Dermatology Service, Eisenhower Army Medical Center, Fort Gordon, Georgia (D.S.W.); Department of Biochemistry and Molecular Biology, Medical College of Georgia, Augusta, Georgia (D.L.); and Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, Georgia (W.B.B., H.S.)
- Address correspondence to:
Dr. Stephen Hsu, Department of Oral Biology and Maxillofacial Pathology, School of Dentistry, AD1443, Medical College of Georgia, Augusta, GA 30912-1126. E-mail address: shsu{at}mail.mcg.edu
Abstract
Autoimmune disorders, characterized by inflammation and apoptosis of target cells leading to tissue destruction, are mediated in part by autoantibodies against normal cellular components (autoantigens) that may be overexpressed. For example, antibodies against the autoantigens SS-A/Ro and SS-B/La are primary markers for systemic lupus erythematosus and Sjögren's syndrome. Recently, studies in animals demonstrated that green tea consumption may reduce the severity of some autoimmune disorders, but the mechanism is unclear. Herein, we sought to determine whether the most abundant green tea polyphenol, (-)-epigallocatechin-3-gallate (EGCG), affects autoantigen expression in human cells. Cultures of pooled normal human primary epidermal keratinocytes and of an immortalized human salivary acinar cell line were incubated with 100 μM EGCG (a physiologically achievable level for topical application or oral administration) for various time periods and then analyzed by cDNA microarray analysis, reverse transcription-polymerase chain reaction, and Western blotting for expression of several major autoantigen candidates. EGCG inhibited the transcription and translation of major autoantigens, including SS-B/La, SS-A/Ro, coilin, DNA topoisomerase I, and α-fodrin. These findings, taken together with green tea's anti-inflammatory and antiapoptotic effects, suggest that green tea polyphenols could serve as an important component in novel approaches to combat autoimmune disorders in humans.
Footnotes
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This study was supported in part by National Cancer Institute, National Institutes of Health Grant R21 CA097258-01A1 and funded through the Department of Oral Biology and Maxillofacial Pathology, School of Dentistry, Medical College of Georgia (Augusta, GA) (to S.H.).
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Article, publication date, and citation information can be found at http://jpet.aspetjournals.org.
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doi:10.1124/jpet.105.090399.
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ABBREVIATIONS: SLE, systemic lupus erythematosus; SS, Sjögren's syndrome; ANA, antinuclear autoantibodies; PARP, poly(ADP)-ribose polymerase; RNP, ribonucleoprotein; RT-PCR, reverse transcription-polymerase chain reaction; GTPP, green tea polyphenol(s); TNF-α, tumor necrosis factor-α; CENP, centomere protein(s); EGCG, generic name: (-)-epigallocatechin-3-gallate, chemical name: (2R,3R)-2-(3,4,5-trihydroxyphenyl)-3,4-dihydro-1(2H)-benzopyran-3,5,7-triol 3-(3,4,5-trihydroxybenzoate); NHEK, normal human epidermal keratinocytes; NS-SV-AC, immortalized human salivary gland acinar cells; OSC2, oral squamous cell carcinoma-2; PM, perfectly matched; MM, mismatched; GAPDH, glyceraldehyde-3-phosphate dehydrogenase; PBS, phosphate-buffered saline; PBST, 0.1% Tween 20 in PBS; IL, interleukin; MES, 4-morpho-lineethanesulfonic acid.
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- Received June 1, 2005.
- Accepted July 20, 2005.
- The American Society for Pharmacology and Experimental Therapeutics
