Prevention of UVB-induced immunosuppression in mice by the green tea polyphenol (–)-epigallocatechin-3-gallate may be associated with alterations in IL-10 and IL-12 production

Abstract

UV exposure of the skin, particularly UVB (290-320 nm), causes adverse biological effects, including alterations in cutaneous immune cells, photoaging and photocarcinogenesis. Several studies have shown that polyphenolic compounds isolated from green tea afford protection against UVB-induced inflammatory responses and photocarcinogenesis in murine models. In this study we show that topical application of (-)-epigallocatechin-3-gallate (EGCG) (3 mg/mouse), a major polyphenolic component of green tea, before a single low dose UVB exposure (72 mJ/cm(2)) to C3H/HeN mice prevented UVB-induced inhibition of the contact hypersensitivity response and tolerance induction to the contact sensitizer 2, 4-dinitrofluorobenzene. Topical application of EGCG before UVB exposure reduced the number of CD11b+ monocytes/macrophages and neutrophils infiltrating into skin inflammatory lesions, which are considered to be responsible for creating the UV-induced immunosuppressive state. In addition, application of EGCG before UVB exposure decreased UVB-induced production of the immunomodulatory cytokine interleukin (IL)-10 in skin as well as in draining lymph nodes (DLN), whereas production of IL-12, which is considered to be a mediator and adjuvant for induction of contact sensitivity, was found to be markedly increased in DLN when compared with UVB alone-exposed mice. Taken together, our data demonstrate that EGCG protects against UVB-induced immunosuppression and tolerance induction by: (i) blocking UVB-induced infiltration of CD11b+ cells into the skin; (ii) reducing IL-10 production in skin as well as in DLN; (iii) markedly increasing IL-12 production in DLN. Protection against UVB-induced immunosuppression by EGCG may be associated with protection against UVB-induced photocarcinogenesis.

Chemoprevention of photocarcinogenesis by selected dietary botanicals

“…EGCG treatment also inhibits the secretion of immunosuppressive cytokine IL-10 at UV irradiated sites as well as in draining lymph nodes compared to those mice which were not treated with EGCG but exposed to UVB radiation. 109 This observation suggests a possible mechanism by which EGCG prevents UVB-induced suppression of the immune system in mice. 109 Simultaneously, IL-12 is another immunoregulatory cytokine and augments the immune responses and possesses antitumor activity.…”

“…109 This observation suggests a possible mechanism by which EGCG prevents UVB-induced suppression of the immune system in mice. 109 Simultaneously, IL-12 is another immunoregulatory cytokine and augments the immune responses and possesses antitumor activity. In the same study, application of EGCG in combination with UVB synergistically increased IL-12 production in regional lymph nodes.…”

“…Since UVB-induced infiltrating leukocytes (CD11b + cells) play a crucial role in UVB-induced suppression of immune responses, we investigated the effect of EGCG on UVB-induced infiltration of CD11b + cells, and it was found that treatment of EGCG results in prevention of UVB-induced immune suppression and tolerance induction which was associated with reduction in the number of infiltrating CD11b + cells at UVB-irradiated sites. 109 Hammerberg et al 130,131 demonstrated that blocking of infiltrating leukocytes using anti-CD11b antibody or treatment with soluble complement receptor type-1 blocked UV-induced immune suppression and tolerance induction in C3H/HeN mice. These results indicate that UV-induced infiltrating CD11b + cells are critical in suppressing the CHS response.…”

Anthocyanin‐ and hydrolyzable tannin‐rich pomegranate fruit extract modulates MAPK and NF‐κB pathways and inhibits skin tumorigenesis in CD‐1 mice

“…Epidermis from the whole skin was separated as described earlier 28 and was homogenized in ice-cold lysis buffer (50 mM Tris-HCl, 150 mM NaCl, 1 mM EGTA, 1 mM EDTA, 20 mM NaF, 100 mM Na 3 VO 4 , 0.5% NP-40, 1% Triton X-100, 1 mM PMSF, pH 7.4) with freshly added protease inhibitor cocktail (Protease Inhibitor Cocktail Set III; Calbiochem, La Jolla, CA). The homgenate was then centrifuged at 14,000g for 25 min at 4°C and the supernatant (total cell lysate) was collected, aliquoted and stored at Ϫ80°C.…”

“…The epidermis from the dissected skin was separated as described earlier 28 and homogenized at 4°C in a glass-to-glass homogenizer in 10 volumes of ODC buffer (50 mM Tris-HCl buffer, pH 7.5, containing 0.1 mM EDTA, 0.1 mM dithiothreitol, 0.1 mM pyridoxal-5-phosphate, 1 mM 2-mercaptoethanol and 0.1% Tween-80). The homogenate was centrifuged at 100,000g at 4°C and the supernatant was used for enzyme determination.…”