cultivating-three-dimensional-reconstructed-human-epidermis-at-large

Cultivating a Three-dimensional Reconstructed Human Epidermis at a Large Scale

A three-dimensional human epidermis model reconstructed from neonatal primary keratinocytes is presented. Herein, a protocol for the cultivation process ...

University of ferrara

The effects of environmental insults on human health are a major global concern. Some of the most noxious pollutants that humans are exposed to include ozone (O ), particulate matter (PM), and cigarette smoke (CS). Since the skin is the first line of defense against environmental insults, it is considered one of the main target organs for the harmful insults of air pollution. Thus, there is solid evidence that skin pathologies such as premature aging, atopic dermatitis (AD), and psoriasis are associated with pollutant exposure; all of these skin conditions are also associated with an altered redox status. Therefore, although the mechanisms of action and concentrations of O , PM, and CS that we are exposed to differ, exposure to all of these pollutants is associated with the development of similar skin conditions due to the fact that all of these pollutants alter redox homeostasis, increasing reactive oxygen species production and oxidative stress. A main product of oxidative stress, induced by exposure to the aforementioned pollutants, is 4-hydroxy-2-nonenal (HNE), which derives from the oxidation of ω-6 polyunsaturated fatty acids. HNE is a highly reactive compound that can form adducts with cellular proteins and even DNA; it is also an efficient cell signaling molecule able to regulate mitogen-activated protein kinase pathways and the activity of redox-sensitive transcription factors such as Nrf2, AP1, and NFκB. Therefore, increased levels of HNE in the skin, in response to pollutants, likely accelerates skin aging and exacerbates existing skin inflammatory conditions; thus, targeting HNE formation could be an innovative cosmeceutical approach for topical applications.

Involvement of 4-hydroxy-2-nonenal in pollution-induced skin damage.

Cigarette smoke stands among the most toxic environmental pollutants and is composed of thousands of chemicals including polycyclic aromatic hydrocarbons (PAHs). Despite restrict cigarette smoking ban in indoor or some outdoor locations, the risk of non-smokers to be exposed to environmental cigarette smoke is not yet eliminated. Beside the well-known effects of cigarette smoke to the respiratory and cardiovascular systems, a growing literature has shown during the last 3 decades its noxious effects also on cutaneous tissues. Being the largest organ as well as the interface between the outer environment and the body, human skin acts as a natural shield which is continuously exposed to harmful exogenous agents. Thus, a prolonged and/or repetitive exposure to significant levels of toxic smoke pollutants may have detrimental effects on the cutaneous tissue by disrupting the epidermal barrier function and by exacerbating inflammatory skin disorders (i.e. psoriasis, atopic dermatitis). With the development of very complex skin tissue models and sophisticated cigarette smoke exposure systems it has become important to better understand the toxicity pathways induced by smoke pollutants in more realistic laboratory conditions to find solutions for counteracting their effects. This review provides an update on the skin models currently available to study cigarette smoke exposure and the known pathways involved in cutaneous toxicity. In addition, the article will briefly cover the inflammatory skin pathologies potentially induced and/or exacerbated by cigarette smoke exposure.

Mimicking cigarette smoke exposure to assess cutaneous toxicity.

Ethosome represents a smart transdermal vehicle suitable for solubilization and cutaneous application of drugs. Coenzyme Q10 is an endogenous antioxidant whose supplementation can counteract many cutaneous disorders and pathologies. In this respect, the present study describes the production, characterization, and cutaneous protection of phosphatidylcholine based ethosomes as percutaneous delivery systems for coenzyme Q10. CoQ10 entrapment capacity in ethosomes was almost 100%, vesicles showed the typical 'fingerprint' structure, while mean diameters were around 270 nm, undergoing an 8% increase after 3 months from production. An ex-vivo study, conducted by transmission electron microscopy, could detect the uptake of ethosomes in human skin fibroblasts and the passage of the vesicles through 3D reconstituted human epidermis. Immunofluorescence analyses were carried on both on fibroblasts and 3D reconstituted human epidermis treated with ethosomes in the presence of HO as oxidative stress challenger, evaluating 4-hydroxynonenal protein adducts which is as a reliable biomarker for oxidative damage. Notably, the pretreatment with CoQ10 loaded in ethosomes exerted a consistent protective effect against oxidative stress, in both models, fibroblasts and in reconstituted human epidermis respectively.

Ethosomes for Coenzyme Q10 Cutaneous Administration: From Design to 3D Skin Tissue Evaluation.

Exposure to air pollutants has been now associated with detrimental effects on a variety of organs, including the heart, lungs, GI tract, and brain. However, recently it has become clear that pollutant exposure can also promote the development/exacerbation of a variety of skin conditions, including premature aging, psoriasis, acne, and atopic dermatitis. Although the molecular mechanisms by which pollutant exposure results in these cutaneous pathological manifestations, it has been noticed that an inflammatory status is a common denominator of all those skin conditions. For this reason, recently, the activation of a cytosolic multiprotein complex involved in inflammatory responses (the inflammasome) that could promote the maturation of proinflammatory cytokines interleukin-1β and interleukin-18 has been hypothesized to play a key role in pollution-induced skin damage. In this review, we summarize and propose the cutaneous inflammasome as a novel target of pollutant exposure and the eventual usage of inflammasome inhibitor as new technologies to counteract pollution-induced skin damage. Possibly, the ability to inhibit the inflammasome activation could prevent cutaneous inflammaging and ameliorate the health and appearance of the skin.

Article	Year
Involvement of 4-hydroxy-2-nonenal in pollution-induced skin damage. BioFactors (Oxford, England)\| PubMed ID: 31087730	2019
Mimicking cigarette smoke exposure to assess cutaneous toxicity. Toxicology in vitro : an international journal published in association with BIBRA\| PubMed ID: 31669394	2020
Ethosomes for Coenzyme Q10 Cutaneous Administration: From Design to 3D Skin Tissue Evaluation. Antioxidants (Basel, Switzerland)\| PubMed ID: 32503293	2020
Inflammasome Activation in Pollution-Induced Skin Conditions. Plastic and reconstructive surgery\| PubMed ID: 33347070	2021

Roxane Prieux

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