T. Mammone

Green Tea Phenol Extracts Reduce UVB‐induced DNA Damage in Human Cells via Interleukin‐12†

Green tea chemoprevention has been a focus of recent research, as a polyphenolic fraction from green tea (GTP) has been suggested to prevent UV radiation‐induced skin cancer. Recently, it was demonstrated that GTP reduced the risk for skin cancer in a murine photocarcinogenesis model. This was accompanied by a reduction in UV‐induced DNA damage. These effects appeared to be mediated via interleukin (IL)‐12, which was previously shown to induce DNA repair. Therefore, we studied whether GTP induction of IL‐12 and DNA repair could also be observed in human cells. KB cells and normal human keratinocytes were exposed to GTP 5 h before and after UVB. UVB‐induced apoptosis was reduced in UVB‐exposed cells treated with GTP. GTP induced the secretion of IL‐12 in keratinocytes. The reduction in UV‐induced cell death by GTP was almost completely reversed upon addition of an anti‐IL‐12‐antibody, indicating that the reduction of UV‐induced cell death by GTP is mediated via IL‐12. The ability of IL‐12 to reduce DNA damage and sunburn cells was confirmed in “human living skin equivalent” models. Hence the previously reported UV‐protective effects of GTP appear to be mediated in human cells via IL‐12, most likely through induction of DNA repair.

Norepinephrine modulates human dendritic cell activation by altering cytokine release

Abstract:  Norepinephrine (NE) can modulate dendritic cell (DC) activation in animal models, but the response of human DC to NE and other response modifiers is as yet not completely understood. Here we report the effect of NE on the cytokine response of a mixed population of human DC cells to extracellular stimuli. These cells were obtained by differentiating human cord blood CD34+ precursor cells. NE inhibited the lipopolysaccharide (LPS)‐stimulated production of interleukin (IL)‐23, IL‐12 p40, tumor necrosis factor (TNF)‐alpha and IL‐6 whereas the expression of IL‐10 was not significantly affected. Thus, human cord blood‐derived DC respond to NE in a manner similar to mouse Langerhans cells (LC). Furthermore, forskolin also inhibited the LPS‐induced levels of TNF‐alpha, IL‐12 p40, IL‐23 p19 and IL‐6, supporting the hypothesis that the effects of NE are mediated by cAMP. Data from experiments using inhibitors of adrenergic receptors suggest that NE acts through beta‐adrenergic receptors. As IL‐23 promotes the differentiation of CD4+ T cells required for TH1‐mediated immunity, we suggest that NE decreases the differentiation of CD4+ T cells needed for TH1‐mediated contact hypersensitivity and that NE is a candidate regulator of human DC functions in the skin.

[55] Noninvasive techniques for measuring oxidation products on the surface of human skin

Publisher Summary Oxidative stress is defined as the result of an imbalance between prooxidants and antioxidants in living cells. This imbalance leads to molecular damage (peroxidation of lipids, metal-catalyzed carbonylation of proteins, and oxidative damage to DNA) as well as to modifications in cellular morphology (zeiosis, modification of chromatin structure) and tissue alterations. One way to illustrate the physiological consequences of oxidative stress imposed on human skin and the relevance of antioxidants is to analyze histology sections before and after an oxidative stress in the presence or absence of antioxidants. Morphological modifications of the ultraviolet-exposed epidermis are remarkable, particularly the loss of cell-to-cell contact and intercellular spongiosis. Protection afforded by the antioxidants against these morphological changes is nearly complete. However, histology methods are invasive and impractical for studies involving large cohorts of volunteers. Noninvasive techniques are therefore preferred for the analysis of the molecular consequences of the oxidative stresses induced by UVA, singlet oxygen, or ozone. For example, one might be interested in learning about the formation of oxidation products on the surface or in the different layers of the epidermis exposed to these environmental factors and its inhibition by antioxidants. This chapter describes some methodologies for investigating the effects of prooxidants and antioxidants on human epidermis.

Age‐dependent response of energy metabolism of human skin to UVA exposure: an in vivo study by 31P nuclear magnetic resonance spectroscopy

Purpose The aim of our study was to evaluate the in vivo energy metabolism of human skin as a function of age, in conditions of rest and after a mild stress caused by a suberythemal UVA irradiation.