scholarly journals Effect of Squalene Monohydroperoxide on Cytotoxicity and Cytokine Release in a Three-Dimensional Human Skin Model and Human Epidermal Keratinocytes

2002 ◽  
Vol 25 (5) ◽  
pp. 605-610 ◽  
Author(s):  
Tadashi Uchino ◽  
Hiroshi Tokunaga ◽  
Hiroshi Onodera ◽  
Masanori Ando
Author(s):  
Jean Christopher Chamcheu ◽  
Stephane Esnault ◽  
Vaqar M. Adhami ◽  
Andrea L. Noll ◽  
Sergette Banang-Mbeumi ◽  
...  

Psoriasis is a chronic immune-mediated skin disease that involves interaction of both immune and skin cells, and is characterized by cytokine-driven epidermal hyperplasia, deviant differentiation, inflammation and angiogenesis. Because available treatments for psoriasis have significant limitations, dietary products are potential natural sources of therapeutic molecules, which can rescind molecular defects associated with psoriasis and could be developed for its management. Fisetin (3,7,3′,4′- tetrahydroxyflavone), a phytochemical naturally found in pigmented fruits and vegetables has demonstrated pro-apoptotic and antioxidant effects in several malignancies. This study utilized biochemical, cellular, pharmacological and tissue-engineering tools to characterize the effects of fisetin on normal human epidermal keratinocytes (NHEKs), peripheral blood mononuclear cells (PBMC) and CD4+ T lymphocytes in 2D and 3D psoriasis-like disease models. Fisetin treatment of NHEKs dose and time-dependently induced differentiation and inhibited interleukin-22-induced proliferation, as well as activation of the PI3K/Akt/mTOR pathway. Fisetin treatment of TNF-α-stimulated NHEKs significantly inhibited the activation of p38 and JNK, but had no effect on ERK1/2. In addition, fisetin treatment significantly decreased the secretion of Th1/Th-17 pro-inflammatory cytokines, particularly IFNγ and IL-17A by 12-O- tetradecanolylphorbol 13-acetate (TPA)-stimulated NHEKs and anti-CD3/CD28-activated human PBMCs. Furthermore, we established the in-vivo relevance of fisetin functions, using a 3D full-thickness human skin model of psoriasis (FTRHSP) that closely mimics in-vivo human psoriatic skin-lesions. Herein, fisetin significantly ameliorated psoriasis-like disease features, and decreased the production of IL-17 by CD4+ T lymphocytes co-cultured with FTRHSP. Collectively, our data identify pro-differentiative, anti-proliferative and anti-inflammatory effects of fisetin, via modulation of PI3K-Akt-mTOR and p38/JNK pathways and the production of cytokines in 2D and 3D human skin model of psoriasis. These results suggest that fisetin has a great potential to be developed as an effective and inexpensive agent for the treatment of psoriasis and other related inflammatory skin disorders.


2008 ◽  
Vol 128 (1) ◽  
pp. 45-50 ◽  
Author(s):  
Tadashi UCHINO ◽  
Toshiaki TAKEZAWA ◽  
Yoshiaki IKARASHI ◽  
Hiroshi TOKUNAGA

2018 ◽  
Vol 53 ◽  
pp. 37-44 ◽  
Author(s):  
Dayane P. uco ◽  
Vânia R. Leite-Silva ◽  
Heron D.T. Silva ◽  
Marcelo D. Duque ◽  
Jeffrey Grice ◽  
...  

Cells ◽  
2019 ◽  
Vol 8 (9) ◽  
pp. 1089 ◽  
Author(s):  
Jean Christopher Chamcheu ◽  
Stephane Esnault ◽  
Vaqar M. Adhami ◽  
Andrea L. Noll ◽  
Sergette Banang-Mbeumi ◽  
...  

Psoriasis is a chronic immune-mediated skin disease that involves the interaction of immune and skin cells, and is characterized by cytokine-driven epidermal hyperplasia, deviant differentiation, inflammation, and angiogenesis. Because the available treatments for psoriasis have significant limitations, dietary products are potential natural sources of therapeutic molecules, which can repair the molecular defects associated with psoriasis and could possibly be developed for its management. Fisetin (3,7,3′,4′-tetrahydroxyflavone), a phytochemical naturally found in pigmented fruits and vegetables, has demonstrated proapoptotic and antioxidant effects in several malignancies. This study utilized biochemical, cellular, pharmacological, and tissue engineering tools to characterize the effects of fisetin on normal human epidermal keratinocytes (NHEKs), peripheral blood mononuclear cells (PBMC), and CD4+ T lymphocytes in 2D and 3D psoriasis-like disease models. Fisetin treatment of NHEKs dose- and time-dependently induced differentiation and inhibited interleukin-22-induced proliferation, as well as activation of the PI3K/Akt/mTOR pathway. Fisetin treatment of TNF-α stimulated NHEKs also significantly inhibited the activation of p38 and JNK, but had enhanced effect on ERK1/2 (MAPK). In addition, fisetin treatment significantly decreased the secretion of Th1/Th-17 pro-inflammatory cytokines, particularly IFN-γ and IL-17A by 12-O-tetradecanolylphorbol 13-acetate (TPA)-stimulated NHEKs and anti-CD3/CD28-activated human PBMCs. Furthermore, we established the in vivo relevance of fisetin functions, using a 3D full-thickness human skin model of psoriasis (FTRHSP) that closely mimics in vivo human psoriatic skin lesions. Herein, fisetin significantly ameliorated psoriasis-like disease features, and decreased the production of IL-17 by CD4+ T lymphocytes co-cultured with FTRHSP. Collectively, our data identify the prodifferentiative, antiproliferative, and anti-inflammatory effects of fisetin, via modulation of the PI3K-Akt-mTOR and p38/JNK pathways and the production of cytokines in 2D and 3D human skin models of psoriasis. These results suggest that fisetin has a great potential to be developed as an effective and inexpensive agent for the treatment of psoriasis and other related inflammatory skin disorders.


2001 ◽  
Vol 23 (5) ◽  
pp. 309-318 ◽  
Author(s):  
K. Schlotmann ◽  
M. Kaeten ◽  
A. F. Black ◽  
O. Damour ◽  
M. Waldmann-Laue ◽  
...  

2004 ◽  
Vol 27 (4) ◽  
pp. 510-514 ◽  
Author(s):  
Kazuhisa Sugimoto ◽  
Takahisa Nishimura ◽  
Koji Nomura ◽  
Kenji Sugimoto ◽  
Takashi Kuriki

Cosmetics ◽  
2019 ◽  
Vol 6 (2) ◽  
pp. 30 ◽  
Author(s):  
Peggy Schlupp ◽  
Thomas Schmidts ◽  
Axel Pössl ◽  
Sören Wildenhain ◽  
Gianni Lo Franco ◽  
...  

Olive trees (Olea europaea) and their processed products, such as olive oil, play a major role in the Mediterranean way of life. Their positive impact on human health is being intensely investigated. One research topic is the identification of new application areas of olive mill wastewater (OMWW). OMWW is characterized by the high content of polyphenols possessing many positive health effects. Thus, the phenol-enriched OMWW extract offers the potential for the treatment of skin disorders and for cosmetic application. The aim of the present study was to evaluate cell viability and proliferation, the anti-inflammatory and anti-oxidative properties of a phenol-enriched OMWW extract on an immortal keratinocyte cell line (HaCaT cells). Moreover, the influence on the growth of various microorganisms was investigated; furthermore, the effects on normal human epidermal keratinocytes (NHEK) and human melanoma cells (A375) were studied in a commercially available tumor invasion skin model. The phenol-enriched OMWW extract showed excellent antimicrobial activity. Moreover, a noticeable reduction in reactive oxygen species formation as well as Interleukin-8 release in HaCaT cells were observed. Finally, the inhibited growth of A375 melanoma nodules in the melanoma skin model could be shown. Our results indicate that the OMWW extract is a promising ingredient for dermal applications to improve skin health and skin protection as well as having a positive impact on skin ageing.


2016 ◽  
Vol 32 (4) ◽  
pp. 311-316 ◽  
Author(s):  
Hyejin Kim ◽  
Jonghye Choi ◽  
Handule Lee ◽  
Juyoung Park ◽  
Byung-Il Yoon ◽  
...  

1998 ◽  
Vol 17 (3) ◽  
pp. 223-229 ◽  
Author(s):  
Elien M. Kurt ◽  
Robert J. Schafer ◽  
Carmen M. Arroyo

The release of the cytokines interleukin (IL)-1α, IL-1β, IL-6, IL-8, and tumor necrosis factor alpha (TNF-α was measured from epiderm alkeratinocytes in an attempt to characterize the immunologic response in keratinocytes following exposure to bis (2-chloroethyl)sulfide (sulfur mustard, HD). Enzyme-linked immunosorbentassay (ELISA) was used to measure cytokine levels in adult and neonatal culture human epidermal keratinocytes (HEK) 3 h after exposure to 0.50 and 1.0 m M HD. A two-way analysis of variance was carried out for cell type and HD concentration. That analysis showed significant differences between cell types for IL-1α and IL-1β(p =.001 and p =.015, respectively). In both of these cytokines, release in neonatal HEK decreased less than in adult HEK. A significant effectof HD concentration was shown only for IL-1β (P <.001), with cytokine release decreasing with increasing HD dose. In addition, a significant cell donor type by HD concentration interaction effect was found for IL-1β under the experimental conditions described in materials and methods. With increasing HD concentration, the relative decrease in cytokine release was much greater for adult than for neonatal HEK.


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