Delta opioid receptor expression correlates to skin ageing and melanin expression in Asian women.

While the evidence for the implication of opioid receptors (OPr) in ageing is growing, there is, to our knowledge, no study focusing directly on changes in vivo cutaneous OPr expression with increasing age. We thus investigated OPr expression in 30 healthy female Asian volunteers in Southern China whose ages range from the early 20s to the early 60s. Excisional biopsies were taken from the sun-exposed extensor area of the lower arm and the photo-protected area of the upper inner arm.

The Opioid Receptor Influences Circadian Rhythms in Human Keratinocytes through the β-Arrestin Pathway.

The recent emphasis on circadian rhythmicity in critical skin cell functions related to homeostasis, regeneration and aging has shed light on the importance of the circadian clock gene as a vital antitumor gene. Furthermore, delta-opioid receptors (DOPrs) have been identified as playing a crucial role in skin differentiation, proliferation and migration, which are not only essential for wound healing but also contribute to cancer development. In this study, we propose a significant association between cutaneous opioid receptor (OPr) activity and circadian rhythmicity.

Distinct transcriptomic and metabolomic profiles characterize NSAID-induced urticaria/angioedema patients undergoing aspirin desensitization.

Background: There is limited data on the mechanisms of aspirin desensitization in patients with nonsteroidal anti-inflammatory drug (NSAID)-induced urticaria/angioedema (NIUA).

Objectives: We sought to characterize the transcriptomic and metabolomic profiles of patients with NIUA undergoing aspirin desensitization.

Methods: PBMCs and plasma were separated from the blood of patients with NIUA undergoing aspirin desensitization for coronary artery disease and NSAID-tolerant controls.

Functionally expressed bitter taste receptor TAS2R14 in human epidermal keratinocytes serves as a chemosensory receptor.

Traditionally, it is theorized that skin sensation is initiated when cutaneous sensory afferents and Merkel cells receive sensory stimuli, while epidermal keratinocytes were deemed to have no role. However, mounting evidence has shown that keratinocytes can initiate skin sensation by receiving sensory stimuli and transmitting sensory information to sensory afferents. Knowledge regarding the mechanisms by which keratinocytes receive exogenous stimuli is limited, with TRP channels and olfactory receptors having been proposed to serve as receptors for exogenous stimuli in keratinocytes.

Progressive expression of PPARGC1α is associated with hair miniaturization in androgenetic alopecia.

Current opinion views androgens as the pathogenic driver in the miniaturization of hair follicles of androgenetic alopecia by interfering with the dermal papilla. This cannot be the sole cause and therefore it is important for therapeutic and diagnostic purposes to identify additional pathways. Comparative full transcriptome profile analysis of the hair bulb region of normal and miniaturized hair follicles from vertex and occipital region in males with and without androgenetic alopecia revealed that next to the androgen receptor as well the retinoid receptor and particularly the PPAR pathway is involved in progressive hair miniaturization.

Microbiome in the hair follicle of androgenetic alopecia patients.

Androgenetic alopecia is the most common form of hair loss in males. It is a multifactorial condition involving genetic predisposition and hormonal changes. The role of microflora during hair loss remains to be understood.

Full-Thickness Human Skin Equivalent Models of Atopic Dermatitis.

Atopic dermatitis is a chronic inflammatory skin disease caused by complex multifactorial etiology. In the recent years, there have been significant advances in tissue engineering and the generation of in vitro skin models representative of healthy and diseased states. This chapter describes the methodology for the fabrication of in vitro human skin equivalent (HSE) from human keratinocytes and fibroblasts using a fibrin-based dermal matrix and serum-free culture conditions.

Investigating endogenous µ-opioid receptors in human keratinocytes as pharmacological targets using novel fluorescent ligand.

Opioids in skin function during stress response, regeneration, ageing and, particularly in regulating sensation. In chronic pruritus, topical treatment with Naltrexone changes μ-opioid receptor (μ-OR) localization to relieve itch. The molecular mechanisms behind the effects of Naltrexone on μ-OR function in reduction of itching behavior has not been studied.

Specific Targeting of Melanotic Cells with Peptide Ligated Photosensitizers for Photodynamic Therapy.

A strategy combining covalent conjugation of photosensitizers to a peptide ligand directed to the melanocortin 1 (MC1) receptor with the application of sequential LED light dosage at near-IR wavelengths was developed to achieve specific cytotoxicity to melanocytes and melanoma (MEL) with minimal collateral damage to surrounding cells such as keratinocytes (KER). The specific killing of melanotic cells by targeted photodynamic therapy (PDT) described in this study holds promise as a potentially effective adjuvant therapeutic method to control benign skin hyperpigmentation or superficial melanotic malignancy such as Lentigo Maligna Melanoma (LMM).

Physiological Doses of Red Light Induce IL-4 Release in Cocultures between Human Keratinocytes and Immune Cells.

Phototherapy is routinely used for the treatment of various skin conditions and targeted therapy of superficial cancers. However, the molecular mechanisms behind their biological effects and the need for efficacy enhancing photosensitizers are not well addressed. Particularly, not much is known about the inherent effect of light from the visible spectrum on cytokine release and its downstream effects in keratinocytes and immune cells located in skin and therefore exposed to light.

Aging in hair follicle stem cells and niche microenvironment.

Hair graying and hair loss are prominent and common characteristics of the elderly population. In some individuals these processes can significantly impact their quality of life, leading to depression, anxiety and other serious mental health problems. Accordingly, there has been much interest in understanding the complex physiological changes within the hair follicle in the aging individual.

Synthetic Peptide Drugs for Targeting Skin Cancer: Malignant Melanoma and Melanotic Lesions.

Peptides play decisive roles in the skin, ranging from host defense responses to various forms of neuroendocrine regulation of cell and organelle function. Synthetic peptides conjugated to radionuclides or photosensitizers may serve to identify and treat skin tumors and their metastatic forms in other organs of the body. In the introductory part of this review, the role and interplay of the different peptides in the skin are briefly summarized, including their potential application for the management of frequently occurring skin cancers.

The Roles of Opioid Receptors in Cutaneous Wound Healing.

The process of recovery from skin wounding can be protracted and painful, and scarring may lead to weakness of the tissue, unpleasant sensations such as pain or itch, and unfavorable cosmetic outcomes. Moreover, some wounds simply fail to heal and become a chronic burden for the sufferer. Understanding the mechanisms underlying wound healing and the concomitant sensory disorders and how they might be manipulated for therapeutic benefit has attracted much interest in recent years, and here we discuss the latest developments in the field, focusing on the emergent roles of the peripheral opioid receptor (OPr) system.

Opioids and skin homeostasis, regeneration and ageing - What's the evidence?

What has the opioid receptor system, known for beneficial as well as disastrous effects in the central nervous system, to do with skin? The question is appropriate considering the fact that the nervous system and the skin both derive from the ectoderm. As part of the skin neuroendocrine system, the opioid receptor system exemplifies the closeness between the nervous system and the skin. Overexpression of the δ-opioid receptor in keratinocytes yields dysregulation of involucrin, loricrin, and filaggrin, proteins essential to the integrity of the skin barrier.

What happens in the skin? Integrating skin permeation kinetics into studies of developmental and reproductive toxicity following topical exposure.

Animal-based developmental and reproductive toxicological studies involving skin exposure rarely incorporate information on skin permeation kinetics. For practical reasons, animal studies cannot investigate the many factors which can affect human skin permeation and systemic uptake kinetics in real-life scenarios. Traditional route-to-route extrapolation is based on the same types of experiments and requires assumptions regarding route similarity.

Fibroblast heterogeneity and its implications for engineering organotypic skin models in vitro.

Advances in cell culture methods, multidisciplinary research, clinical need to replace lost skin tissues and regulatory need to replace animal models with alternative test methods has led to development of three dimensional models of human skin. In general, these in vitro models of skin consist of keratinocytes cultured over fibroblast-populated dermal matrices. Accumulating evidences indicate that mesenchyme-derived signals are essential for epidermal morphogenesis, homeostasis and differentiation.

Evaluation of the applicability of the Immuno-solid-phase allergen chip (ISAC) assay in atopic patients in Singapore.

Background/objective: Molecular-based allergy diagnostics are gaining popularity in clinical practice. Our aim was to evaluate their role in the tropics, given the inherent genetic and environmental differences.

Methods: We recruited subjects with history of atopy and collected data on demographics and atopic symptoms using validated questionnaires.

The role of opioid receptors in migration and wound recovery in vitro in cultured human keratinocytes and fibroblasts.

We have previously described significant changes in skin differentiation and the delay in wound healing from delta-opioid receptor knockout mice. In addition, we have shown that opioid receptor ligands and their receptor systems affect wound healing in vitro and the migration pattern of human skin cells, such as keratinocytes and fibroblasts (Bigliardi-Qi et al., Differentiation 74:174-185, 2006; Bigliardi et al.

The δ-opioid receptor affects epidermal homeostasis via ERK-dependent inhibition of transcription factor POU2F3.

Neuropeptides and their receptors are present in human skin, and their importance for cutaneous homeostasis and during wound healing is increasingly appreciated. However, there is currently a lack of understanding of the molecular mechanisms by which their signaling modulates keratinocyte function. Here, we show that δ-opioid receptor (DOPr) activation inhibits proliferation of human keratinocytes, resulting in decreased epidermal thickness in an organotypic skin model.

Opioids and the skin--where do we stand?

The common ectodermal origin of the skin and nervous systems can be expected to predict likely interactions in the adult. Over the last couple of decades much progress has been made to elucidate the nature of these interactions, which provide multidirectional controls between the centrally located brain and the peripherally located skin and immune system. The opioid system is an excellent example of such an interaction and there is growing evidence that opioid receptors (OR) and their endogenous opioid agonists are functional in different skin structures, including peripheral nerve fibres, keratinocytes, melanocytes, hair follicles and immune cells.

Treatment of pruritus with topically applied opiate receptor antagonist.

Background: Pruritus is the most common and distressing skin symptom, and treatment of itch is a problem for thousands of people. The currently available therapies are not very effective. Therefore there is an urgent need to find new effective topical drugs against itching.