scholarly journals The psoriatic shift induced by interleukin 17 is promptly reverted by a specific anti-IL-17A agent in a three-dimensional organotypic model of normal human skin culture

2020 ◽  
Vol 64 (2) ◽  
Author(s):  
Elena Donetti ◽  
Giulia Lombardo ◽  
Serena Indino ◽  
Laura Cornaghi ◽  
Francesca Arnaboldi ◽  
...  
Keyword(s):  
Human Skin ◽  
Three Dimensional ◽  
Aesthetic Surgery ◽  
Clinical Effectiveness ◽  
Control Group ◽  
Interleukin 17 ◽  
Normal Human Skin ◽  
Transmission Electron Microscopy Analysis ◽  
Keratinocyte Proliferation ◽  
Normal Human

Interleukin 17A (IL-17A), mainly produced by the T helper subclass Th17, plays a key role in the psoriatic plaque formation and progression. The clinical effectiveness of anti-IL-17A agents is documented, but the early and specific mechanisms of their protection are not identified yet. The challenge of the present study is to investigate the possible reversal exerted by a specific anti-IL-17A agent on the psoriatic events induced by IL-17A in a three-dimensional organotypic model of normal human skin. Bioptic skin fragments obtained after aesthetic surgery of healthy women (n=5) were incubated with i) IL-17A biological inhibitor (anti-IL-17A), ii) IL-17A, iii) a combination of IL-17A and its specific IL-17A biological inhibitor (COMBO). A Control group was in parallel cultured and incubation lasted for 24 and 48 h epidermal-side-up at the air-liquid interface. All subjects were represented in all experimental groups at all considered time-points. Keratinocyte proliferation and the presence of epidermal Langerhans cells were quantitatively estimated. In parallel with transmission electron microscopy analysis, immunofluorescence studies for the epidermal distribution of keratin (K)10, K14, K16, K17, filaggrin/occludin, Toll-like Receptor 4, and Nuclear Factor kB were performed. IL-17A inhibited cell proliferation and induced K17 expression, while samples incubated with the anti-IL-17A agent were comparable to controls. In the COMBO group the IL-17A-induced effects were almost completely reverted. Our study, for the first time, elucidates the most specific psoriatic cellular events that can be partially affected or completely reverted by a specific anti-IL-17A agent during the early phases of the plaque onset and progression. On the whole, this work contributes to expand the knowledge of the psoriatic tableau.

Interleukin 22 early affects keratinocyte differentiation, but not proliferation, in a three-dimensional model of normal human skin

2016 ◽  
Vol 345 (2) ◽  
pp. 247-254 ◽  
Author(s):  
Elena Donetti ◽  
Laura Cornaghi ◽  
Francesca Arnaboldi ◽  
Federica Landoni ◽  
Paolo Romagnoli ◽  
...  
Keyword(s):  
Human Skin ◽  
Three Dimensional ◽  
Keratinocyte Differentiation ◽  
Dimensional Model ◽  
Three Dimensional Model ◽  
Normal Human Skin ◽  
Interleukin 22 ◽  
Normal Human

scholarly journals Effect of Pentacyclic Triterpenoids-Rich Callus Extract of Chaenomeles japonica (Thunb.) Lindl. ex Spach on Viability, Morphology, and Proliferation of Normal Human Skin Fibroblasts

Molecules ◽  
2018 ◽  
Vol 23 (11) ◽  
pp. 3009 ◽  
Author(s):  
Małgorzata Kikowska ◽  
Małgorzata Chmielewska ◽  
Agata Włodarczyk ◽  
Elżbieta Studzińska-Sroka ◽  
Jerzy Żuchowski ◽  
...  
Keyword(s):  
Human Skin ◽  
Proliferation Rate ◽  
Skin Fibroblasts ◽  
Total Phenolic ◽  
Control Group ◽  
Human Skin Fibroblasts ◽  
Normal Human Skin ◽  
Pentacyclic Triterpenoids ◽  
Antioxidant Power ◽  
Normal Human

The effect of the well-characterized callus extract of Chaenomeles japonica on viability, morphology, and proliferation of normal human skin fibroblasts was investigated. The phytochemical analysis was performed using the ultra-high performance liquid chromatography method. The total phenolic, phenolic acid, and flavonoid contents were determined spectrophotometrically. The antioxidant activity was investigated using the DPPH (1,1-Diphenyl-1-picrylhydrazyl Radical Scavenging), FRAP (Ferric Reducing Antioxidant Power), and CUPRAC (CUPric Reducing Antioxidant Capacity) assays. The callus growth index during passages was high as well as the content of pentacyclic triterpenoids. The microscopic observations of the fibroblast viability, morphology and the evaluation of the proliferation ratio (xCELLigence system) proved that the influence of callus extract on the fibroblasts was dose-dependent. The evaluated level of fibroblasts proliferation rate after 72 h of incubation with callus extract at concentration 12.5 µg L−1 was the highest compared to all the analyzed ligands. Moreover, callus extract administrated for 72 h caused a significant increase in the proliferation rate in comparison with the control group (5.7 ± 0.1 vs. 4.4 ± 0.9; p < 0.01). The preliminary studies carried out may suggest that the callus extract rich in triterpenoids may be a potential source of cosmetic ingredients with a beneficial effect on human skin.

Reconstructed Human Epidermis In Vitro: An Alternative to Animal Testing

1995 ◽  
Vol 23 (1) ◽  
pp. 97-110 ◽  
Author(s):  
Maria Ponec
Keyword(s):  
Human Skin ◽  
Three Dimensional ◽  
Structural Features ◽  
Animal Testing ◽  
Normal Human Skin ◽  
Normal Human ◽  
Biochemical Mechanisms ◽  
Human Skin Models

Various three-dimensional human skin models, in which the epidermis exhibits in vivo-like morphological and functional characteristics, have recently been developed. Such models are currently being used to study the development and physiology of the skin, the processes involved in wound healing, and the reactivity of skin to environmental and chemical insults. Since these models reproduce to a large extent the barrier function properties of normal human skin, they can be used for screening potential skin irritants. These substances can be applied topically and their irritant potential can be evaluated using various endpoints, such as the induction of tissue damage or the release of various pro-inflammatory mediators. Studies with human skin equivalents can therefore contribute to our knowledge of the basic biochemical mechanisms underlying irritant reactions, and can be used to understand the structural features of molecules which may be responsible for eliciting an irritant reaction. In addition”, the generation of epidermal equivalents populated with melanocytes, as well as keratinocytes, makes it possible to study the regulation of melanogenesis, melanocyte–keratinocyte interactions, and how these are affected by UV irradiation. Such a model can also be used for testing the phototoxic or photoprotective potentials of various compounds and sunscreens.

The Effect of Practolol, In Vitro Generated Metabolites of Practolol and Chemical Analogues on the Rate of Growth of Human Skin Fibroblasts

1984 ◽  
Vol 12 (2) ◽  
pp. 89-97
Author(s):  
Graham R. Elliott ◽  
H.E. Amos ◽  
James W. Bridges
Keyword(s):  
Human Skin ◽  
Psoriasis Patient ◽  
Skin Fibroblasts ◽  
Human Skin Fibroblasts ◽  
Cell Type ◽  
Normal Human Skin ◽  
Rate Of Growth ◽  
Structural Analogues ◽  
Normal Human

The rate of growth of normal human skin fibroblasts was inhibited in a dose related, reversible, fashion by practolol (N-4-(2-hydroxy)-3 (1-methyl)-aminopropoxyphenylacetamine) (ID50 1.35 ± 0.14 x 10-3M), propranolol (1-(isopropylamino)-3(1-naphthyl-oxy)-2-propranolol) (ID50 0.145 ± 0.02 x 10-3M) and paracetamol (N-(4-hydroxyphenyl) acetamide) (ID50 0.85 ± 0.2 x 10-3M). Skin fibroblasts isolated from a psoriasis patient were more sensitive towards practolol (ID50 0.48 ± 0.14 x 10-3M) and propranolol (ID50 0.032 ± 0.002 x 10-3M), but less sensitive towards paracetamol (ID50 1.3 ± 0.07 x 10-3M). In vitro generated metabolites of practolol, using normal or Arochlor 1254-pretreated hamster liver preparations, and structural analogues of practolol had no effect upon the growth of either cell type.

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