Particulate Matter-Induced Aryl Hydrocarbon Receptor Regulates Autophagy in Keratinocytes

Kang

et al. 2020

IJMS

Aryl hydrocarbon receptor (AhR) and autophagy reportedly regulate immune responses in the skin. This study explored the effects of AhR activation on autophagy in human keratinocytes, and the relevance of AhR and autophagy in psoriasis pathogenesis. AhR activation by 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) repressed autophagy, while autophagy inhibition induced AhR activation in HaCaT cells and normal human epidermal keratinocytes (NHEKs). A particularly strong interaction between AhR and autophagy was observed in proinflammatory cytokines-stimulated keratinocytes, an in vitro model of psoriasis. In skin biopsies from psoriasis patients, a similar impact of AhR on autophagy and inflammation was observed. AhR inhibition blocked TCDD-and chloroquine-induced p65NF-κB and p38MAPK phosphorylation in proinflammatory cytokines-stimulated HaCaT cells. Moreover, higher expression of AhR and CYP1A1, and lower expression of LC3, were detected in psoriatic skin tissues, compared to the controls. These data demonstrated that AhR modulated autophagy leads to skin inflammation in human keratinocytes via the p65NF-κB/p38MAPK signaling pathways, suggesting that AhR signaling and autophagy might be involved in the pathogenesis of chronic inflammatory disorders such as psoriasis.

Section: Discussionmentioning

confidence: 99%

Role of Aryl Hydrocarbon Receptor Activation and Autophagy in Psoriasis-Related Inflammation

Kang

et al. 2020

IJMS

“…CYP enzymes can metabolize PAHs, and the formed metabolites can induce cell damage either by the formation of DNA, protein adducts, or the generation of ROS [195,[204][205][206][207][208]. Indeed, PM upregulates the CYP enzyme mRNA and protein expression in vitro and in vivo [119,128,129,134,135,139,141,167,171,172,178,187]. Other ROS producing enzymes are the members of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) family [209].…”

Section: Pm Triggers Exogenous and Endogenous Ros Formationmentioning

confidence: 99%

Impact of airborne particulate matter on skin: a systematic review from epidemiology to in vitro studies

Dijkhoff¹,

Drašler²,

Karakoçak³

et al. 2020

Part Fibre Toxicol

120

116

Background: Air pollution is killing close to 5 million people a year, and harming billions more. Air pollution levels remain extremely high in many parts of the world, and air pollution-associated premature deaths have been reported for urbanized areas, particularly linked to the presence of airborne nano-sized and ultrafine particles. Main text: To date, most of the research studies did focus on the adverse effects of air pollution on the human cardiovascular and respiratory systems. Although the skin is in direct contact with air pollutants, their damaging effects on the skin are still under investigation. Epidemiological data suggested a correlation between exposure to air pollutants and aggravation of symptoms of chronic immunological skin diseases. In this study, a systematic literature review was conducted to understand the current knowledge on the effects of airborne particulate matter on human skin. It aims at providing a deeper understanding of the interactions between air pollutants and skin to further assess their potential risks for human health. Conclusion: Particulate matter was shown to induce a skin barrier dysfunction and provoke the formation of reactive oxygen species through direct and indirect mechanisms, leading to oxidative stress and induced activation of the inflammatory cascade in human skin. Moreover, a positive correlation was reported between extrinsic aging and atopic eczema relative risk with increasing particulate matter exposure.

“…The highly lipophilic PAHs contained in PM 2.5 are major factors leading to mutagenicity [5] and easily penetrate the skin [6]. The aromatic hydrocarbon receptor (AhR) is activated by PM in the epidermis [7]. Upon activation by PAHs, AhR may increase the production of intracellular reactive oxygen species (ROS) [8].…”

Section: Introductionmentioning

confidence: 99%

Particulate Matter 2.5 Mediates Cutaneous Cellular Injury by Inducing Mitochondria-Associated Endoplasmic Reticulum Stress: Protective Effects of Ginsenoside Rb1

et al. 2019

The prevalence of fine particulate matter-induced harm to the human body is increasing daily. The aim of this study was to elucidate the mechanism by which particulate matter 2.5 (PM2.5) induces damage in human HaCaT keratinocytes and normal human dermal fibroblasts, and to evaluate the preventive capacity of the ginsenoside Rb1. PM2.5 induced oxidative stress by increasing the production of reactive oxygen species, leading to DNA damage, lipid peroxidation, and protein carbonylation; this effect was inhibited by ginsenoside Rb1. Through gene silencing of endoplasmic reticulum (ER) stress-related genes such as PERK, IRE1, ATF, and CHOP, and through the use of the ER stress inhibitor tauroursodeoxycholic acid (TUDCA), it was demonstrated that PM2.5-induced ER stress also causes apoptosis and ultimately leads to cell death; however, this phenomenon was reversed by ginsenoside Rb1. We also found that TUDCA partially restored the production of ATP that was inhibited by PM2.5, and its recovery ability was significantly higher than that of ginsenoside Rb1, indicating that the process of ER stress leading to cell damage may also occur via the mitochondrial pathway. We concluded that ER stress acts alone or via the mitochondrial pathway in the induction of cell damage by PM2.5, and that ginsenoside Rb1 blocks this process. Ginsenoside Rb1 shows potential for use in skin care products to protect the skin against damage by fine particles.