interleukin-8 and ascorbate-2-phosphate

Uneven skin pigmentation is a significant cosmetic concern, and the identification of topically applicable molecules to address this issue is of general interest. We report that the tetrapeptide PKEK (Pro-Lys-Glu-Lys) can exert skin whitening effects based on one in vitro and four double-blinded vehicle-controlled in vivo studies. (i) Treatment of human keratinocytes with PKEK significantly reduced UVB-stimulated mRNA expression of interleukin (IL)-6, IL-8 and TNF-α and, most importantly, proopiomelanocorticotropin (POMC), i.e. a gene encoding the pigmentation-inducing soluble mediator α- (α-MSH). (ii) PKEK treatment significantly inhibited UVB-induced upregulation of genes encoding for IL-1α, IL-6, IL-8, TNF-α as well as POMC and tyrosinase in 10 healthy volunteers pretreated with PKEK for 4 weeks once daily. (iii) In a study enrolling 39 Caucasian women, facial pigment spots significantly faded after 6 weeks when PKEK was combined with the skin whitener sodium ascorbyl phosphate (SAP), whereas PKEK or SAP alone led to less pronounced fading of the pigment spots. (iv) Addition of PKEK enhanced the skin whitening potency of a SAP-containing preparation if applied for 8 weeks to the back of hands of 19 Caucasians. (v) 27 Japanese women were treated on their faces twice daily with an SAP only or a PKEK+SAP-containing formulation for 8 weeks. Application of PKEK+SAP significantly reduced skin pigmentation by 26% and by 18% according to SCINEXA score. We demonstrate that PKEK has the capacity to reduce UVB-induced skin pigmentation and may be suited to serve as a skin tone-modulating agent in cosmetic products.

Topics: Adult; Aged; Ascorbic Acid; Asian People; Cells, Cultured; Colorimetry; Double-Blind Method; Female; Gene Expression; Humans; Interleukin-1beta; Interleukin-6; Interleukin-8; Keratinocytes; Male; Middle Aged; Monophenol Monooxygenase; Oligopeptides; Pro-Opiomelanocortin; Skin; Skin Aging; Skin Pigmentation; Treatment Outcome; Tumor Necrosis Factor-alpha; Ultraviolet Rays; White People

An innovative lyophilized dry powder formulation consisting of urea-crosslinked hyaluronic acid (HA-CL) and sodium ascorbyl phosphate (SAP) - LYO HA-CL - SAP- was prepared and characterized in vitro for physico-chemical and biological properties. The aim was to understand if LYO HA-CL - SAP could be used as adjuvant treatment for nasal inflammatory diseases. LYO HA-CL - SAP was suitable for nasal delivery and showed to be not toxic on human nasal septum carcinoma-derived cells (RPMI 2650 cells) at the investigated concentrations. It displayed porous, polygonal particles with unimodal, narrow size distribution, mean geometric diameter of 328.3 ± 27.5 µm, that is appropriate for nasal deposition with no respirable fraction and 88.7% of particles with aerodynamic diameter >14.1 µm. Additionally, the formulation showed wound healing ability on RPMI 2650 cells, and reduced interleukin-8 (IL-8) level in primary nasal epithelial cells pre-induced with lipopolysaccharide (LPS). Transport study across RPMI 2650 cells showed that HA-CL could act not only as carrier for SAP and active ingredient itself, but potentially also as mucoadhesive agent. In conclusion, these results suggest that HA-CL and SAP had anti-inflammatory activity and acted in combination to accelerate wound healing. Therefore, LYO HA-CL - SAP could be a potential adjuvant in nasal anti-inflammatory formulations.

Topics: Adjuvants, Immunologic; Administration, Intranasal; Adult; Anti-Inflammatory Agents; Ascorbic Acid; Cell Line; Cell Survival; Epithelial Cells; Humans; Hyaluronic Acid; Interleukin-8; Lipopolysaccharides; Nasal Mucosa; Powders; Urea; Wound Healing; Young Adult

Acne is the most common inflammatory skin disease. Interleukin-1 (IL-1) is at the beginning of the cytokine signaling cascade and may be involved in the pathogenesis of this disorder. It activates redox-sensitive transcription factors, which induce IL-6 and IL-8 expression. Interestingly, L-ascorbyl-2-phosphate (APS) was shown to have beneficial effects in patients with acne vulgaris. The mechanism of action of this agent remains unknown. Here, we investigated if APS attenuates IL-1β- or TNF-α-mediated IL-6 and IL-8 expression in SZ95 sebocytes, whereas TNF-α was used as control. We also explored NF-κB activation which is known to orchestrate IL-1β- and TNF-α-mediated cytokine expression in many cell types. Both IL-1β and TNF-α increased IL-6 and IL-8 mRNA expression in SZ95 sebocytes. However, only IL-1β induced IL-6 and IL-8 secretion. IL-1β but not TNF-α activated NF-κB canonical signaling as demonstrated by Iκ-Bα phosphorylation and degradation as well as by nuclear accumulation of NF-κB/p65. Concomitant treatment of SZ95 sebocytes with APS attenuated the effect of IL-1β and TNF-α on IL-6 and IL-8 gene expression as well as on IL-1β-mediated NF-κB signaling. In contrast, APS failed to reduce IL-1β-mediated IL-6 and IL-8 secretion, presumably by maintained IL-1β-mediated p38 activation, which is known to control IL-8 secretion. Our findings shed light into the impact of IL-1β on the inflammatory cytokine response and its molecular mechanisms in human sebocytes. Our data further suggest that the beneficial effect of APS in acne patients involves attenuation of NF-κB signaling but not reduction of IL-6 or IL-8 secretion.

Topics: Ascorbic Acid; Cell Line; Cell Survival; Gene Expression Regulation; Humans; Interleukin-1beta; Interleukin-6; Interleukin-8; NF-kappa B; RNA, Messenger; Signal Transduction; Tumor Necrosis Factor-alpha

L-Ascorbic acid 2-phosphate magnesium salt (APM) is an L-ascorbic acid (AsA) derivative developed to improve AsA stability and display effective biochemical characteristics. This study aimed to investigate the effects of APM on the functions and properties of human gingival fibroblasts with respect to the prevention of periodontal disease in comparison with those of AsA.. Human gingival fibroblasts were incubated in the presence or absence of APM or L-ascorbic acid sodium salt (AsANa). Intracellular AsA was analysed by HPLC. Collagen synthesis was measured by ELISA and real-time RT-PCR. Intracellular reactive oxygen species (ROS) induced by hydrogen peroxide (H(2)O(2)) were quantified using a fluorescence reagent, and cell damage was estimated with calcein acetoxymethyl ester. Furthermore, intracellular ROS induced by tumor necrosis factor-α (TNF-α) were quantified, and expression of TNF-α-induced interleukin-8 expression, which increases due to inflammatory reactions, was measured by ELISA and real-time RT-PCR.. APM remarkably and continuously enhanced intracellular AsA and promoted type 1 collagen synthesis and mRNA expression. Furthermore, APM decreased cell damage through the suppression of H(2)O(2)-induced intracellular ROS and inhibited interleukin-8 production through the suppression of TNF-α-induced intracellular ROS. These effects of APM were superior to those of AsANa.. These results suggest that APM is more effective than AsANa in terms of intake, collagen synthesis, decreasing cell damage and inhibiting interleukin-8 expression in human gingival fibroblasts. This suggests that local application of APM can help to prevent periodontal disease.

Topics: Anti-Inflammatory Agents; Antioxidants; Ascorbic Acid; Cell Line; Cell Proliferation; Cell Survival; Cells, Cultured; Chromatography, High Pressure Liquid; Collagen Type I; Fibroblasts; Fluoresceins; Fluorescent Dyes; Free Radical Scavengers; Gingiva; Humans; Hydrogen Peroxide; Interleukin-8; Reactive Oxygen Species; Tumor Necrosis Factor-alpha

Adipose tissue serves as a source of adipokines and cytokines with both local and systemic actions in health and disease. In this study, we examine the hypothesis that multipotent human adipose-derived stem cells (ASCs), capable of differentiating along the adipocyte, chondrocyte, and osteoblast pathways, contribute to adipose tissue-derived cytokine secretion. Following exposure to basic fibroblast growth factor (bFGF) or epidermal growth factor (EGF), the ASCs significantly increase their secretion of hepatocyte growth factor (HGF), a cytokine implicated in hematopoiesis, vasculogenesis, and mammary epithelial duct formation. Ascorbic acid synergizes with these inductive factors, further increasing HGF levels. Following exposure to lipopolysaccharide, ASCs increase their secretion of both hematopoietic (granulocyte/monocyte, granulocyte, and macrophage colony stimulating factors, interleukin 7) and proinflammatory (interleukins 6, 8, and 11, tumor necrosis factor alpha) cytokines based on ELISA and RT-PCR. In co-cultures established with umbilical cord blood-derived CD34(+) cells, the ASCs support long-term hematopoiesis in vitro. Furthermore, in short-term 12-day co-cultures, the ASC maintain and expand the numbers of both myeloid and lymphoid progenitors. These observations are consistent with the functionality of the secreted cytokines and confirm recent reports by other laboratories concerning the hematopoietic supportive capability of ASCs. We conclude that the ASCs display cytokine secretory properties similar to those reported for bone marrow-derived mesenchymal stem cells (MSCs).

Topics: Adipocytes; Adipose Tissue; Adult; Adult Stem Cells; Angiogenic Proteins; Ascorbic Acid; Cell Differentiation; Cell Proliferation; Cells, Cultured; Coculture Techniques; Cytokines; Endothelial Cells; Epidermal Growth Factor; Female; Fibroblast Growth Factor 2; Granulocyte Colony-Stimulating Factor; Granulocyte-Macrophage Colony-Stimulating Factor; Hematopoiesis; Hematopoietic Stem Cells; Hepatocyte Growth Factor; Humans; Inflammation Mediators; Interleukin-11; Interleukin-6; Interleukin-7; Interleukin-8; Lipopolysaccharides; Middle Aged; Multipotent Stem Cells; Paracrine Communication; RNA, Messenger; Time Factors; Tumor Necrosis Factor-alpha