Effects of hydroquinone on whole-genome scale transcription of human epidermal keratinocytes.
Ontology highlight
ABSTRACT: Hydroquinone (HQ) is a well-known phenolic compound that causes chemical leukoderma. Hydroquinone was once used as photographic developers for films and papers, and it is widely used as a topical application in skin whitening to reduce the color of skin. Recently, the United States Food and Drug Administration (US FDA) banned all over-the-counter products with hydroquinone due to its potential toxicity. Topical cream with hydroquinone up to 4% should be prescribed and used with specific caution. In this study, to elucidate the toxicological role of keratinocyte in the pathogenesis of chemical leukoderma, we analyzed genome-wide transcriptional data of cultured human epidermal keratinocytes (HEKs) treated with sub-cytotoxic hydroquinone concentration.
Project description:We have previously shown that nano-sized graphene oxide (NGO) displays anti-inflammatory activities against natural killer T (NKT) cell-mediated sepsis. To address whether NGO could be applied to treat acute skin inflammation. We developed a conventional skin Cetaphil® cream containing NGO (NGO cream) for topical application to skin lesions and investigated its therapeutic efficacy by employing the tape-stripping-induced acute skin inflammation model. Topical application of NGO cream to the wounded area significantly reduced skin lesions compared with the control cream. Moreover, NGO cream treatment prevented the tape-stripping-elicited infiltration of and IL1β production by skin neutrophils and dendritic cells (DCs). Furthermore, such anti-inflammatory effects of NGO cream were attributed to decreased infiltration of IL12-producing DCs and IFNγ-producing cells (e.g., CD4+ T, CD8+ T, γδ T, NK, and NKT cells) into the skin. In addition, topical NGO cream administration enhanced the expression of suppressive molecules such as FR4 on skin regulatory T cells. Through RNA sequencing analysis, we found that the preventive effect of NGO cream on acute skin inflammation may be correlated with the activation of keratinocytes located in the epidermis. Our results support NGO cream as a therapeutic option to control acute skin inflammation.
Project description:Ceramides in the stratum corneum (SC) play an important role in the epidermal barrier function. We focused on these functions and developed a synthetic pseudo-ceramide for medical (SPCM)-containing steroid cream [SPCM (+)]. This cream forms films on the skin surface with multilamellar structures, like the human SC, and exerts anti-inflammatory effects through steroids. However, the preventive effects of this cream on disruption of skin barrier remain unclear. This study aimed to analyze the efficacy of SPCM (+) using human three-dimensional (3D) skin models.
Project description:miR-146a acts as a negative feedback regulator of inflammation. To investigate the role of miR-146a in psoriasis psoriasiform skin inflammation was indeuced in Mir-146a-/- and wild type mice (C57BL6J) by topical applciation of imiquimod (IMQ)-cream (Aldara). Gene expression profiling (Affymetrix) was used to identify transcriptomic changes associated with psoriasis-like skin inflammation in wild type vs. miR-146a -/-mice. A daily topical dose of 31.25 mg of Aldara cream (5% IMQ) was applied on the right ear of miR-146a -/- and C57BL/6 mice on three consecutive days to induce psorisis-like skin inflammation. Mice were sacrificed at day 4. Ear flaps were collected for total RNA extraction and hybridization on Affymatrix GeneTitan plate format Gene ST 2.1 (mouse).
Project description:Psoriasis is a chronic inflammatory skin disorder that is predominantly characterized by sharply demarcated chronic erythematous plaques. Although its etiological mechanisms are largely unknown, recent evidence suggests that the topical application of imiquimod (IMQ) cream causes psoriasis-like skin inflammation in humans and mice. Skin examined 4 hours after IMQ cream treatment. Results provide insight into the role of each knockout mice phenotype in the response to IMQ-induced psoriasis model.
Project description:Low concentrations of the dissolved leonardite humic acid HuminFeed® (HF) prolonged the lifespan and enhanced the thermal stress resistance of the model organism Caenorhabditis elegans. Furthermore growth was impaired and reproduction delayed, effects which have also been identified in other polyphenolic monomers, including tannic acid, rosmarinic acid, and caffeic acid. Moreover, a chemical modification of HF (HF-HQ), which increases its phenolic/quinonoid moieties, magnified the biological impact on C. elegans. To gain a deep insight into the molecular basis of these effects, we performed global transcriptomics on young adult (3 d) and old adult (11 d) nematodes exposed to two concentrations of HF and young adults (3 d) exposed to two concentrations of HF-HQ. The global transcriptome was compared in Caenorhabditis elegans mutant strain GE24, pha-1(e2123) exposed to 0, 0.2 and 2.0 mM HuminFeed® (HF) or Huminfeed-Hydroquinone (HF-HQ). Nematodes were harvested as 3 or 11 day old adults (for HF) or 3 day old adults (for HF-HQ).
Project description:miR-146a acts as a negative feedback regulator of inflammation. To investigate the role of miR-146a in psoriasis psoriasiform skin inflammation was indeuced in Mir-146a-/- and wild type mice (C57BL6J) by topical applciation of imiquimod (IMQ)-cream (Aldara). Gene expression profiling (Affymetrix) was used to identify transcriptomic changes associated with psoriasis-like skin inflammation in wild type vs. miR-146a -/-mice.
Project description:The goal of the study is to examine changes in tumor gene expression after imiquimod treatment. RNA was extracted from spontaneous tumors in control mice (n=4) and in imiquimod-treated mice (n=4). Gene expression was compared between the control group and the treated group. In the imiquimod treatment group, the mice received topical treatment of 5% imiquimod cream (Aldara) on shaved skin at the site of spontaneous tumors for one treatment cycle (3 consecutive days). RNA was extracted from 4 spontaneous tumors from neu-tg mice treated with topical imiquimod for 1 cycle and 4 spontaneous tumors from control mice
Project description:Analysis of whole mouse brain following peripheral, cutaneous immune stimulation with Aldara cream or aquaeous control cream. Results provide insight into the central response to peripheral inflammation Microarrays were used to investigate the global gene expression of mouse brains following peripheral, cutaneous application of Aldara cream or control cream C57BL/6 mice were treated with 80mg topical Aldara cream or aquaeous control cream every 24 hours for 5 consecutive days. 24 hours following the final application, brains were removed and RNA was extracted using RNeasy Mini Kit (Qiagen). 5 brains from each group were analysed using full genome Affymetrix GeneChip array
Project description:Identification of chemical allergen inducible genes in mouse skin. Ear samples were isolated from CL57BL/6 mice 6 hours after topical application of a prototypic chemical allergen, a skin irritant or vehicle alone. Total RNA were extracted from ear skin samples treated with a chemical allergen, a skin irritant, or vehicle alone for 6 hours.
Project description:Identification of chemical allergen inducible genes in mouse skin. Ear samples were isolated from CL57BL/6 mice 6 hours after topical application of a prototypic chemical allergen, a skin irritant or vehicle alone.