Polypodium leucotomos inhibits ultraviolet B radiation-induced immunosuppression.

BACKGROUND: An extract of the tropical fern Polypodium leucotomos (PL) administered orally to mice inhibits ultraviolet B (UVB) radiation-induced skin cancer formation. UVB-induced murine skin cancers occur, in part, because of UVB-induced immunosuppression. Thus, we examined whether PL inhibits UVB-suppression of the induction of contact hypersensitivity (CHS) locally or systemically. METHODS: C57BL/6 mice received standard drinking water or water-containing PL. In the local model, mice were shaved on the dorsum and exposed to 3500 J/m(2) of UVB radiation daily for 4 days. Control mice were not irradiated. After the last irradiation they were sensitized to oxazolone topically at the irradiated site. To examine the ability of PL to inhibit systemic UVB-induced immunosuppression, mice were given 10,000 J/m(2) of UVB radiation once and immunized at a non-exposed site 3 days later. Six days after immunization (in both models), mice were challenged on the ears with oxazolone and 24/48 h ear swelling assessed. RESULTS: PL in drinking water significantly reduced the inhibition of CHS observed with exposure to UVB radiation in both the local and systemic models. CONCLUSIONS: The ability of PL to inhibit UVB radiation-induced immune suppression may explain, in part, its ability to inhibit UVR-induced skin cancer induction in mice.

Augmentation of cutaneous immune responses by ATP gamma S: purinergic agonists define a novel class of immunologic adjuvants.

Extracellular nucleotides activate ligand-gated P2XR ion channels and G protein-coupled P2YRs. In this study we report that intradermal administration of ATPgammaS, a hydrolysis-resistant P2 agonist, results in an enhanced contact hypersensitivity response in mice. Furthermore, ATPgammaS enhanced the induction of delayed-type hypersensitivity to a model tumor vaccine in mice and enhanced the Ag-presenting function of Langerhans cells (LCs) in vitro. Exposure of a LC-like cell line to ATPgammaS in the presence of LPS and GM-CSF augmented the induction of I-A, CD80, CD86, IL-1beta, and IL-12 p40 while inhibiting the expression of IL-10, suggesting that the immunostimulatory activities of purinergic agonists in the skin are mediated at least in part by P2Rs on APCs. In this regard, an LC-like cell line was found to express mRNA for P2X(1), P2X(7), P2Y(1), P2Y(2), P2Y(4), P2Y(9), and P2Y(11) receptors. We suggest that ATP, when released after trauma or infection, may act as an endogenous adjuvant to enhance the immune response, and that P2 agonists may augment the efficacy of vaccines.

Dietary lutein reduces ultraviolet radiation-induced inflammation and immunosuppression.

Ultraviolet radiation (UVR) promotes skin cancer development by mutagenic, immunosuppressive, and oxidative-stress-inducing mechanisms; however, certain antioxidants may counteract and prevent UVR-induced photodamage. Lutein is a xanthophyll carotenoid with potent antioxidant activity. Because reactive oxygen species (ROS) are believed to have a role in UVR-induced skin damage, we investigated whether lutein can modify UVR effects including the tissue swelling response to midrange UVR (280-320 nm, ultraviolet B (UVB) radiation) and UVB suppression of contact hypersensitivity (CHS) in both the local and the systemic models of UV-induced immunosuppression. We found that compared to mice fed the standard laboratory diet, mice fed dietary lutein demonstrated significant inhibition of ear swelling owing to UVB radiation. Mice exposed to 1700 J per m2 UVB radiation four times at daily intervals and then sensitized to dinitrofluorobenzene at the site of irradiation showed a decreased CHS response upon challenge. This suppression by UVB radiation was significantly inhibited by lutein feeding. When UVB radiation was given at a single dose of 10,000 J per m2 to inhibit the induction of CHS at a distant, nonirradiated site, no effect of lutein was seen. Finally, lutein accumulated in the skin of mice following diet supplementation and was shown to decrease ROS generation following UVR exposure. Thus, lutein modulates the skin's response to UVR and may contribute to the defense against some of the deleterious effects of solar radiation.