Effects of native and particulate polyphenols on DNA damage and cell viability after UV-C exposure.

Plant polyphenols have poor water solubility, resulting in low bioavailability. In order to overcome this limitation, the drug molecules can be coated with multiple layers of polymeric materials. Microcrystals of quercetin and resveratrol coated with a (PAH/PSS) or (CH/DexS) shell were prepared using the layer-by-layer assembly method; cultured human HaCaT keratinocytes were treated with UV-C, and after that, cells were incubated with native and particulate polyphenols.

DNA Repair Activation and Cell Death Suppression by Plant Polyphenols in Keratinocytes Exposed to Ultraviolet Irradiation.

This work investigated effects of plant polyphenolic compounds (PPs) on responses of cultured human HaCaT keratinocytes to ultraviolet radiation in the C range (UV-C). The experimental data obtained indicate a cytoprotective effect of PPs added immediately after UV-C exposure. The efficiency of PPs was lowered in the following order: acacetin ≥ silybin > quercetin.

Effects of pre- and post-treatment with plant polyphenols on human keratinocyte responses to solar UV.

Background: The understanding of the anti-inflammatory mechanisms of action of plant polyphenols (PPs) and clarification of the relationship between their anti-inflammatory and antioxidant properties may result in a new therapeutic approach to skin cancers.

Objective: To elucidate the underlying mechanism, we analyzed the ability of PPs to attenuate inflammatory, metabolic and oxidative cellular responses to UV irradiation.

Methods: Normal human epidermal keratinocytes (NHEK) were exposed to physiologically relevant dose of solar-simulated UV irradiation.

Plant polyphenols regulate chemokine expression and tissue repair in human keratinocytes through interaction with cytoplasmic and nuclear components of epidermal growth factor receptor system.

Aims: To evaluate mechanisms underlying modulation of inflammatory chemokines in primary human keratinocytes (normal human epidermal keratinocytes) and repair-related processes in wound models by plant polyphenols (PPs) with antioxidant and superoxide scavenging properties (verbascoside [Vb], resveratrol [Rv], polydatin [Pd], quercetin [Qr], and rutin).

Results: Epidermal growth factor receptor (EGFR)-controlled chemokines CXCL8/interleukin 8 (IL-8), CCL2/monocyte chemotactic protein-1 (MCP-1), and CXCL10/interferon gamma-produced protein of 10 kDa (IP-10) were modulated by transforming growth factor alpha (TGF-α) and by the tumor necrosis factor alpha/interferon gamma combination (T/I). EGFR phosphorylation, nuclear translocation, and downstream cytoplasmic signaling pathways (extracellular regulation kinase [ERK]1/2, p38, STAT3, and PI-3K) were studied.

Plant polyphenols differentially modulate inflammatory responses of human keratinocytes by interfering with activation of transcription factors NFκB and AhR and EGFR-ERK pathway.

Molecular mechanisms underlying modulation of inflammatory responses in primary human keratinocytes by plant polyphenols (PPs), namely the glycosylated phenylpropanoid verbascoside, the stilbenoid resveratrol and its glycoside polydatin, and the flavonoid quercetin and its glycoside rutin were evaluated. As non-lethal stimuli, the prototypic ligand for epidermal growth factor receptor (EGFR) transforming growth factor alpha (TGFalpha), the combination of tumor necrosis factor (TNFalpha) and interferon (IFNgamma) (T/I), UVA+UVB irradiation, and bacterial lipopolysaccharide (LPS) were used. We demonstrated differential modulation of inflammatory responses in keratinocytes at signal transduction, gene transcription, and protein synthesis levels as a function of PP chemical structure, the pro-inflammatory trigger used, and PP interaction with intracellular detoxifying systems.

Differential modulation of stress-inflammation responses by plant polyphenols in cultured normal human keratinocytes and immortalized HaCaT cells.

Background: Environmental and endogenous stresses to skin are considered causative reasons for skin cancers, premature ageing, and chronic inflammation. Screening of substances with preventive and/or curative properties is currently based on mechanistic studies of their effects towards stress-induced responses in skin cell cultures.

Objective: We compared effects of plant polyphenols (PPs) on the constitutive, UVA-, LPS-, or TNF-alpha-induced inflammatory responses in cultured normal human epidermal keratinocytes (NHEK) and immortalized HaCaT cells.

Antioxidant and signal modulation properties of plant polyphenols in controlling vascular inflammation.

Oxidized low-density lipoproteins (oxLDL) play a critical role in the initiation of atherosclerosis through activation of inflammatory signaling. In the present work we investigated the role of antioxidant and signal modulation properties of plant polyphenols in controlling vascular inflammation. Significant decrease in intracellular NO level and superoxide overproduction was found in human umbilical vein endothelial cells (HUVEC) treated with oxLDL, but not with LDL.

Glutathione peroxidase activity in the blood cells of psoriatic patients correlates with their responsiveness to Efalizumab.

Biological treatment of psoriasis, a chronic inflammatory immune-mediated pathology of huge social impact, has become a recent revolutionizing breakthrough in the management of the disease. Apart from anti-TNF-alpha biologics, recombinant proteins-inhibitors of the T lymphocytes-antigen presenting cells interaction, Efalizumab among them, have been successfully used in the therapy of psoriasis. Serious concern regarding safety and efficacy of biologics remains because they induce numerous adverse effects and a significant number of patients are non-responders.

Dysfunction of glutathione S-transferase leads to excess 4-hydroxy-2-nonenal and H(2)O(2) and impaired cytokine pattern in cultured keratinocytes and blood of vitiligo patients.

Oxidative stress due to increased epidermal levels of H(2)O(2) with consequent inhibition of catalase activity is generally accepted as a leading cytotoxic mechanism of melanocyte loss in vitiligo. Keratinocyte-derived cytokines are considered key factors in the maintenance of melanocyte structure and functions. We hypothesized that abnormal redox control may lead to impaired cytokine production by keratinocytes, thus causing noncytotoxic defects in melanocyte proliferation and melanogenesis.

Mechanisms of the suppression of free radical overproduction by antioxidants.

In accordance with the mechanism of suppression of free radical overproduction in biological systems all antioxidants can be divided into two main groups: chain-breaking antioxidants and preventive antioxidants. Chain-breaking antioxidants, often referred to as free radical scavengers, protect against oxidative stress as a result of scavenging initial, peroxyl and rarely alkyl radicals. Preventive antioxidants act as chelators of transition metals, inhibitors of enzymatic systems responsible for the generation of reactive oxygen species (ROS) or reduce hydrogen peroxides and organic hydroperoxides and can prevent an appearance of initiating radical and frustrate a free radical chain reaction from ever setting in motion.

Recognition of live phosphatidylserine-labeled tumor cells by dendritic cells: a novel approach to immunotherapy of skin cancer.

Dendritic cells (DC) loaded with tumor antigens from apoptotic/necrotic tumor cells are commonly used as vaccines for cancer therapy. However, the use of dead tumor cells may cause both tolerance and immunity, making the effect of vaccination unpredictable. To deliver live tumor "cargoes" into DC, we developed a new approach based on the "labeling" of tumors with a phospholipid "eat-me" signal, phosphatidylserine.

Oxidation and cytotoxicity of 6-OHDA are mediated by reactive intermediates of COX-2 overexpressed in PC12 cells.

Parkinson's disease is characterized by a progressive loss of dopaminergic neurons, likely associated with dysregulation of oxidation of catechols, such as dopamine (DA) and 6-hydroxydopamine (6-OHDA), and resulting in oxidative stress. The involvement of cyclooxygenase-2 (COX-2) in pathogenesis of Parkinson's disease has been suggested. However, specific COX-2 triggered mechanisms participating in catalysis of DA oxidation and enhanced catechol-induced cytotoxicity remain poorly characterized.

Unusual inflammatory and fibrogenic pulmonary responses to single-walled carbon nanotubes in mice.

Single-walled carbon nanotubes (SWCNT) are new materials of emerging technological importance. As SWCNT are introduced into the life cycle of commercial products, their effects on human health and environment should be addressed. We demonstrated that pharyngeal aspiration of SWCNT elicited unusual pulmonary effects in C57BL/6 mice that combined a robust but acute inflammation with early onset yet progressive fibrosis and granulomas.

Oxidative lipidomics of apoptosis: redox catalytic interactions of cytochrome c with cardiolipin and phosphatidylserine.

The primary life-supporting function of cytochrome c (cyt c) is control of cellular energetic metabolism as a mobile shuttle in the electron transport chain of mitochondria. Recently, cyt c's equally important life-terminating function as a trigger and regulator of apoptosis was identified. This dreadful role is realized through the relocalization of mitochondrial cyt c to the cytoplasm where it interacts with Apaf-1 in forming apoptosomes and mediating caspase-9 activation.