Prevention of ultraviolet radiation-induced immunosuppression by (-)-epigallocatechin-3-gallate in mice is mediated through interleukin 12-dependent DNA repair.

Abstract

PURPOSE:

Solar UV radiation-induced immunosuppression is considered to be a risk factor for melanoma and nonmelanoma skin cancers. We previously have shown that topical application of (-)-epigallocatechin-3-gallate (EGCG) prevents UV-induced immunosuppression in mice. We studied whether prevention of UV-induced immunosuppression by EGCG is mediated through interleukin 12 (IL-12)-dependent DNA repair.

EXPERIMENTAL DESIGN:

IL-12 knockout (KO) mice on C3H/HeN background and DNA repair-deficient cells from xeroderma pigmentosum complementation group A (XPA) patients were used in this study. The effect of EGCG was determined on UV-induced suppression of contact hypersensitivity and UV-induced DNA damage in the form of cyclobutane pyrimidine dimers (CPD) in mice and XPA-deficient cells using immunohistochemistry and dot-blot analysis.

RESULTS:

Topical treatment with EGCG prevented UV-induced suppression of the contact hypersensitivity in wild-type (WT) mice but did not prevent it in IL-12 KO mice. Injection of anti-IL-12 monoclonal antibody to WT mice blocked the preventive effect of EGCG on UV-induced immunosuppression. EGCG reduced or repaired UV-induced DNA damage in skin faster in WT mice as shown by reduced number of CPDs(+) cells and reduced the migration of CPD(+) antigen-presenting cells from the skin to draining lymph nodes. In contrast, this effect of EGCG was not seen in IL-12 KO mice. Further, EGCG was able to repair UV-induced CPDs in XPA-proficient cells obtained from healthy person but did not repair in XPA-deficient cells, indicating that nucleotide excision repair mechanism is involved in DNA repair.

CONCLUSIONS:

These data identify a new mechanism by which EGCG prevents UV-induced immunosuppression, and this may contribute to the chemopreventive activity of EGCG in prevention of photocarcinogenesis.

• Authors: Syed M Meeran, Sudheer K Mantena, Santosh K Katiyar
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 12 Issue 7 Pt 1 Pg. 2272-80 (Apr 01 2006) ISSN: 1078-0432 [Print] United States
• PMID: 16609044 (Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Anticarcinogenic Agents
• Interleukin-12
• Catechin
• epigallocatechin gallate

Topics

• Administration, Topical
• Animals
• Anticarcinogenic Agents (administration & dosage, pharmacology)
• Catechin (administration & dosage, analogs & derivatives, pharmacology)
• Cells, Cultured
• DNA Repair (radiation effects)
• Genotype
• Humans
• Immune System (drug effects, radiation effects)
• Immune Tolerance (drug effects, immunology, radiation effects)
• Interleukin-12 (deficiency, genetics, radiation effects)
• Mice
• Mice, Inbred C3H
• Mice, Knockout
• Sensitivity and Specificity
• Ultraviolet Rays (adverse effects)