scholarly journals The Effect of Cannabidiol on UV-Induced Changes in Intracellular Signaling of 3D-Cultured Skin Keratinocytes

2021 ◽  
Vol 22 (3) ◽  
pp. 1501
Author(s):  
Agnieszka Gęgotek ◽  
Sinemyiz Atalay ◽  
Adelina Rogowska-Wrzesińska ◽  
Elżbieta Skrzydlewska

Human epidermal keratinocytes are constantly exposed to UV radiation. As a result, there is a significant need for safe and effective compounds to protect skin cells against this environmental damage. This study aimed to analyze the effect of phytocannabinoid-cannabinoid (CBD)-on the proteome of UVA/B irradiated keratinocytes. The keratinocytes were cultured in a three-dimensional (3D) system, designed to mimic epidermal conditions closely. The obtained results indicate that CBD protected against the harmful effects of UVA/B radiation. CBD decreased the expression of proinflammatory proteins, including TNFα/NFκB and IκBKB complex and decreased the expression of proteins involved in de novo protein biosynthesis, which are increased in UVA/B-irradiated cells. Additionally, CBD enhanced the UV-induced expression of 20S proteasome subunits. CBD also protected protein structures from 4-hydroxynonenal (HNE)-binding induced by UV radiation, which primarily affects antioxidant enzymes. CBD-through its antioxidant/anti-inflammatory activity and regulation of protein biosynthesis and degradation-protects skin cells against UVA/B-induced changes. In the future, its long-term use in epidermal cells should be investigated.

Nanomaterials ◽  
2020 ◽  
Vol 10 (5) ◽  
pp. 992
Author(s):  
Javier Jiménez-Lamana ◽  
Simon Godin ◽  
Gerard Aragonès ◽  
Cinta Bladé ◽  
Joanna Szpunar ◽  
...  

Although nickel allergy and carcinogenicity are well known, their molecular mechanisms are still uncertain, thus demanding studies at the molecular level. The nickel carcinogenicity is known to be dependent on the chemical form of nickel, since only certain nickel compounds can enter the cell. This study investigates, for the first time, the cytotoxicity, cellular uptake, and molecular targets of nickel nanoparticles (NiNPs) in human skin cells in comparison with other chemical forms of nickel. The dose-response curve that was obtained for NiNPs in the cytotoxicity assays showed a linear behavior typical of genotoxic carcinogens. The exposure of keratinocytes to NiNPs leads to the release of Ni2+ ions and its accumulation in the cytosol. A 6 kDa nickel-binding molecule was found to be synthesized by cells exposed to NiNPs at a dose corresponding to medium mortality. This molecule was identified to be tumor-related p63-regulated gene 1 protein.


1995 ◽  
Vol 128 (6) ◽  
pp. 1209-1219 ◽  
Author(s):  
N A Hotchin ◽  
A Gandarillas ◽  
F M Watt

Integrins of the beta 1 family play a central role in controlling adhesion and terminal differentiation within the epidermis. When human epidermal keratinocytes undergo terminal differentiation, intracellular transport of newly synthesized integrins is inhibited, and mature receptors are lost from the cell surface. We have examined the mechanisms underlying these processes, using an experimental model in which keratinocytes are placed in suspension to induce terminal differentiation. The block in intracellular transport was keratinocyte- and integrin-specific since it was not observed when fibroblasts were placed in suspension and did not affect E-cadherin synthesis in suspended keratinocytes. Newly synthesized beta 1 integrins associated with an endoplasmic reticulum resident protein, calnexin; the association was prolonged when keratinocytes were placed in suspension, suggesting a role for calnexin in the inhibition of transport. After 24 h, the level of beta 1 integrin mRNA declines in suspended keratinocytes, reflecting inhibition of gene transcription, but in fibroblasts, the level remained constant. Transport of integrins could be blocked in both adherent keratinocytes and fibroblasts by inhibiting total protein synthesis, raising the possibility that transport is coupled to de novo integrin synthesis. The fate of receptors on the surface of keratinocytes was followed by confocal immunofluorescence microscopy, immunoelectron microscopy, and biochemical analysis: with the onset of terminal differentiation, endocytosed receptors were transported to the lysosomes. These experiments reveal novel mechanisms by which integrin levels can be controlled. Together with our earlier evidence for transcriptional regulation and affinity modulation of integrins, they highlight the complexity of the mechanisms which ensure that the onset of terminal differentiation is linked to detachment of keratinocytes from the underlying basement membrane.


Cosmetics ◽  
2020 ◽  
Vol 7 (3) ◽  
pp. 66 ◽  
Author(s):  
Hélène Ozanne ◽  
Hechmi Toumi ◽  
Benoît Roubinet ◽  
Ludovic Landemarre ◽  
Eric Lespessailles ◽  
...  

Laminarin, a β-(1,3)-glucan from the seaweed Laminaria digitata, is a polysaccharide which provides anti-inflammatory and anti-oxidative properties. Its influence on both human dermal fibroblasts adult (HDFa) and normal human epidermal keratinocytes (NHEK) has not been established yet. Herein, laminarin effects were examined on skin cells’ mitochondrial and antioxidant activities. Cytokines, hyaluronic acid, and procollagen type I secretions and interaction mechanisms were explored after a maximum of 72 h treatment with laminarin. Our results demonstrated a decrease in mitochondrial activities with 72 h treatment with laminarin from 500 µg.mL−1 for NHEK cells and from 100 µg.mL−1 for HDFa cells without cytotoxicity. No variation of hyaluronic acid or type I procollagen was observed for all laminarin concentrations, while an antioxidant effect was found against reactive oxygen species (ROS) from 1 µg.mL−1 for HDFa cells in both H2O2 and UVA radiation conditions, and from 10 µg.mL−1 and 1 µg.mL−1 for NHEK cells in both H2O2 and UVA radiation conditions, respectively. Laminarin treatment modulated both cells surface glycosylation and cytokine secretions of skin cells. Overall, our data suggest a positive effect of β-(1,3)-glucan on skin cells on oxidative stress and inflammation induced by environmental factors. Of note, these effects are through the modulation of glycan and receptors interactions at the skin cells surface.


Nano LIFE ◽  
2014 ◽  
Vol 04 (01) ◽  
pp. 1440002 ◽  
Author(s):  
Rehab M. Amin ◽  
Abuelmagd Abdelmonem ◽  
Thomas Verwanger ◽  
Elsayed Elsherbini ◽  
Barbara Krammer

Magnetic nanoparticles have received considerable attention in nanomedicine due to their potential application as therapeutic or diagnostic tools based on their particular properties. However, prior to clinical application investigating the effect of these nanoparticles on cells is essential. The aim of the following study is therefore to evaluate the cytotoxicity of magnetic ( Fe 3 O 4) and gold-coated magnetic nanoparticles ( Fe 3 O 4@ Au ) on various cell lines in order to clarify the risk of these materials for human use. Toxicity of these nanoparticles on human dermal fibroblasts (SKIN), human squamous cell carcinoma cells (A431 cells) and human epidermal keratinocytes ( HaCaT cells) were determined using the MTT assay. Results showed that, within the used concentration range, Fe 3 O 4 nanoparticles had no significant effect on all investigated cell lines, while Fe 3 O 4@ Au nanoparticles seem to have a moderate toxicity on all cell lines with some selectivity for the malignant cells, although it is yet moderate. The different characteristic of the cell lines' survival with respect to incubation time and nanoparticle concentration could be partly due to different cell death modes. Therefore, the prepared Fe 3 O 4 nanoparticles are harmless and could be applied safely for skin cancer treatment or diagnosis.


2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Noo Ri Lee ◽  
Beom Jun Kim ◽  
Chung Hyeok Lee ◽  
Young Bin Lee ◽  
Solam Lee ◽  
...  

AbstractGlucocorticoids (GCs) are potent anti-inflammatory drugs, the secretion of which is mediated and controlled by the hypothalamic–pituitary–adrenal axis. However, they are also secreted de novo by peripheral tissues for local use. Several tissues express 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1), including the skin. The inactive GC cortisone is converted by 11β-HSD1 to active GC cortisol, which is responsible for delayed wound healing during a systemic excess of GC. However, the role of 11β-HSD1 in inflammation is unclear. We assessed whether 11β-HSD1 affects the development of atopic dermatitis (AD) in vitro and in vivo. The expression of 11β-HSD1 in the epidermis of AD lesions was higher than that in the epidermis of healthy controls. Knockdown of 11β-HSD1 in human epidermal keratinocytes increased the production of thymic stromal lymphopoietin. In an oxazolone-induced mouse model of AD, localized inhibition of 11β-HSD1 aggravated the development of AD and increased serum cytokine levels associated with AD. Mice with whole-body knockout (KO) of 11β-HSD1 developed significantly worse AD upon induction by oxazolone. We propose that 11β-HSD1 is a major factor affecting AD pathophysiology via suppression of atopic inflammation due to the modulation of active GC in the skin.


Author(s):  
Robert Bajgar ◽  
Anna Moukova ◽  
Nela Chalupnikova ◽  
Hana Kolarova

Background: The sun is a natural source of UV radiation. It can be divided into three bands, UVA (315–400 nm), UVB (280–315 nm) and UVC (100–280 nm), where the radiation up to 290 nm is very effectively eliminated by the stratospheric ozone. Although UV radiation can have a beneficial effect on our organism and can be used in the treatment of several skin diseases, it must primarily be considered harmful. Methods: In the presented work, we focused on the study of the longer-wavelength UV components (UVA and UVB) on the human epidermal keratinocyte line HaCaT. As UVA and UVB radiation sources, we used commercially available UVA and UVB tubes from Philips (Philips, Amsterdam, The Netherlands), which are commonly employed in photochemotherapy. We compared their effects on cell viability and proliferation, changes in ROS production, mitochondrial function and the degree of DNA damage. Results: Our results revealed that UVB irradiation, even with significantly lower irradiance, caused greater ROS production, depolarization of mitochondrial membrane potential and greater DNA fragmentation, along with significantly lowering cell viability and proliferative capacity. Conclusions: These results confirm that UV radiation causes severe damages in skin cells, and they need to be protected from it, or it needs to be applied more cautiously, especially if the component used is UVB.


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