scholarly journals Topical Treatment of Colquhounia Root Relieves Skin Inflammation and Itch in Imiquimod-Induced Psoriasiform Dermatitis in Mice

2022 ◽  
Vol 2022 ◽  
pp. 1-15
Author(s):  
Fei Li ◽  
Dan Han ◽  
Bo Wang ◽  
Wentao Zhang ◽  
Yan Zhao ◽  
...  
Keyword(s):  
Inflammatory Cytokines ◽  
Neurogenic Inflammation ◽  
Chinese Herb ◽  
Clinical Manifestations ◽  
Skin Lesions ◽  
Oncostatin M ◽  
Inflammatory Factors ◽  
Epidermal Keratinocytes ◽  
Human Epidermal Keratinocytes

Itch is one of the major clinical manifestations of psoriasis, which is closely related with neurogenic inflammation and difficult to control. Colquhounia Root (CR) is a Chinese herb exhibiting broad bioactivities on anti-inflammation. This study was designed to explore the antipsoriatic and anti-itch potential of CR and its underlying mechanisms. Mice in a model of imiquimod-induced psoriasiform dermatitis were treated topically with CR for 7 days, and the severity of skin lesions and itch was significantly ameliorated. CR reduced the inflammatory cell infiltration, as well as mast cells in skins. Particularly, the expression of inflammatory cytokines and chemokine including Il17a, Il22, and Ccl20 and itch-related molecules such as SP, CGRP, and NGF in lesions were decreased in diseased mice upon application with CR. The normal human epidermal keratinocytes were stimulated with the M5 cytokine cocktail, the mixture of IL-17A, IL-22, Oncostatin M, IL-1α, and TNF-α, and cell viability and mRNA expression levels of inflammatory factors and itch-related molecules were measured after being treated with CR. We found that CR inhibited both cell hyperproliferation and overexpression of inflammatory cytokines and itch-related molecules in vitro. Altogether, we conclude that CR relieves psoriatic lesions and itch via controlling immunological and neurogenic inflammation.

scholarly journals RASSF1A Regulates the Abnormal Cell Proliferation in Psoriasis via Inhibition of YAP

2020 ◽  
Author(s):  
Jinjing Jia ◽  
Ning Wang ◽  
Yan Zheng ◽  
Xiumei Mo ◽  
Yu Zhang ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Inflammatory Cytokines ◽  
Skin Lesions ◽  
Oncostatin M ◽  
Negative Regulator ◽  
Inflammatory Factors ◽  
Epidermal Keratinocytes ◽  
Lentivirus Vector ◽  
Rassf1a Methylation

Abstract Background: Psoriasis is a chronic, inflammatory skin disease with high incidence, treatment resistance, and high recurrence. Currently, the exact etiology and pathogenesis are unclear. The goal of this study was to characterize the role of the upstream negative regulator RAS-association domain family 1A (RASSF1A) on Yes-associated protein (YAP) in psoriasis.Methods: Skin lesions of 22 psoriasis patients and 19 normal skin tissue controls were used. Human epidermal keratinocytes were stimulated with M5 (IL-1 α, IL-17, IL-22, TNF-α, oncostatin M), to establish the psoriatic cell model. Methylation inhibitor, 5-Aza-CdR was prepared at different concentrations (5, 10, 20 μmol/L). Cells were infected with lentivirus vector overexpressing RASSF1A. Twenty-five 6-8-week-old female BALB/c mice were used to establish the psoriatic mouse model. Mice were randomly divided into five groups: control (Vaseline applied daily), psoriasis (imiquimod applied daily), and the three different 5-Aza-CdR concentrations (applied daily with imiquimod). Methylation specific PCR (MSP) was used to detect RASSF1A methylation, and immunohistochemistry was used to detect RASSF1A expression in skin lesions. After adding 5-Aza-CdR or lentivirus vector overexpressing RASSF1A, YAP expression, cell proliferation, cell cycle, apoptosis, inflammatory cytokines and related signal pathway activity were detected.Results: As RASSF1A methylation level increased, its expression in psoriasis patients and mice with skin lesions decreased. Addition of 5-Aza-CdR or lentivirus vector overexpressing RASSF1A increased the expression of RASSF1A, reduced the expression of YAP and inflammatory cytokines, cell proliferation, as well as AKT, ERK, STAT3 and NF-κB signaling pathway activities, induced cell cycle arrest in G0/G1 phase, increased apoptosis, and improved skin lesions.Conclusions: RASSF1A inhibited the proliferation of psoriatic cells, induced apoptosis, and reduced the expression of inflammatory factors by inhibiting YAP expression. Based on our findings, targeted drugs that can inhibit RASSF1A methylation and increase its expression may be useful in the treatment of psoriasis.

scholarly journals RASSF1A regulates the abnormal cell proliferation in psoriasis via inhibition of YAP

2020 ◽  
Author(s):  
Jinjing Jia ◽  
Ning Wang ◽  
Yan Zheng ◽  
Xiumei Mo ◽  
Yu Zhang ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Inflammatory Cytokines ◽  
Skin Lesions ◽  
Oncostatin M ◽  
Negative Regulator ◽  
Inflammatory Factors ◽  
Epidermal Keratinocytes ◽  
Lentivirus Vector ◽  
Rassf1a Methylation

Abstract Background: Psoriasis is a chronic, inflammatory skin disease with high incidence, treatment resistance, and high recurrence. Currently, the exact etiology and pathogenesis of psoriasis are unclear. The goal of this study was to characterize the effect of the upstream negative regulator RAS-association domain family 1A (RASSF1A) on Yes-associated protein (YAP) in psoriasis. Methods: Skin lesions of 22 patients with psoriasis and 19 controls with normal skin tissue were used. Human epidermal keratinocytes were stimulated with M5 (IL-1 α, IL-17, IL-22, TNF-α, oncostatin M) to establish the psoriatic cell model. Methylation inhibitor 5-Aza-CdR was prepared at different concentrations (5, 10, 20 μmol/L). Cells were infected with lentivirus vector overexpressing RASSF1A. Twenty-five 6–8-week-old female BALB/c mice were used to establish the psoriatic mouse model. Mice were randomly divided into five groups: control (Vaseline applied daily), psoriasis (imiquimod applied daily), and the three different 5-Aza-CdR concentrations (applied daily with imiquimod). Methylation-specific PCR (MSP) was used to detect RASSF1A methylation and immunohistochemistry was used to detect RASSF1A expression in skin lesions. After adding 5-Aza-CdR or lentivirus vector overexpressing RASSF1A, YAP expression, cell proliferation, cell cycle, apoptosis, inflammatory cytokines, and related signal pathway activity were investigated. Results: As RASSF1A methylation level increased, its expression in patients with psoriasis and mice with skin lesions decreased. Addition of 5-Aza-CdR or lentivirus vector overexpressing RASSF1A increased the expression of RASSF1A, reduced the expression of YAP and inflammatory cytokines, cell proliferation, as well as AKT, ERK, STAT3, and NF-κB signaling pathway activities, induced cell cycle arrest in G0/G1 phase, increased apoptosis, and improved skin lesions. Conclusions: RASSF1A inhibited the proliferation of psoriatic cells, induced apoptosis, and reduced the expression of inflammatory factors by inhibiting YAP expression. Based on our findings, targeted drugs that can inhibit RASSF1A methylation and increase its expression may be useful in the treatment of psoriasis.

scholarly journals Multifaceted Analysis of IL-23A- and/or EBI3-Including Cytokines Produced by Psoriatic Keratinocytes

2021 ◽  
Vol 22 (23) ◽  
pp. 12659
Author(s):  
Kota Tachibana ◽  
Nina Tang ◽  
Hitoshi Urakami ◽  
Ai Kajita ◽  
Mina Kobashi ◽  
...  
Keyword(s):  
Critical Role ◽  
Immunohistochemical Analysis ◽  
Skin Lesions ◽  
Enzyme Linked Immunosorbent Assay ◽  
Epidermal Keratinocytes ◽  
Human Epidermal Keratinocytes ◽  
Barr Virus ◽  
Normal Human ◽  
Epstein Barr

Interleukin (IL) 23 (p19/p40) plays a critical role in the pathogenesis of psoriasis and is upregulated in psoriasis skin lesions. In clinical practice, anti-IL-23Ap19 antibodies are highly effective against psoriasis. IL-39 (p19/ Epstein-Barr virus-induced (EBI) 3), a newly discovered cytokine in 2015, shares the p19 subunit with IL-23. Anti-IL-23Ap19 antibodies may bind to IL-39; also, the cytokine may contribute to the pathogenesis of psoriasis. To investigate IL23Ap19- and/or EBI3-including cytokines in psoriatic keratinocytes, we analyzed IL-23Ap19 and EBI3 expressions in psoriasis skin lesions, using immunohistochemistry and normal human epidermal keratinocytes (NHEKs) stimulated with inflammatory cytokines, using quantitative real-time polymerase chain reaction (RT-PCR), enzyme-linked immunosorbent assay (ELISA), and liquid chromatography-electrospray tandem mass spectrometry (LC-Ms/Ms). Immunohistochemical analysis showed that IL-23Ap19 and EBI3 expressions were upregulated in the psoriasis skin lesions. In vitro, these expressions were synergistically induced by the triple combination of tumor necrosis factor (TNF)-α, IL-17A, and interferon (IFN)-γ, and suppressed by dexamethasone, vitamin D3, and acitretin. In ELISA and LC-Ms/Ms analyses, keratinocyte-derived IL-23Ap19 and EBI3, but not heterodimeric forms, were detected with humanized anti-IL-23Ap19 monoclonal antibodies, tildrakizumab, and anti-EBI3 antibodies, respectively. Psoriatic keratinocytes may express IL-23Ap19 and EBI3 proteins in a monomer or homopolymer, such as homodimer or homotrimer.

scholarly journals Epidermal Growth Factor Relieves Inflammatory Signals inStaphylococcus aureus-Treated Human Epidermal Keratinocytes and Atopic Dermatitis-Like Skin Lesions in Nc/Nga Mice

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Sun Young Choi ◽  
You Jin Lee ◽  
Ji Min Kim ◽  
Hyun Ji Kang ◽  
Sang Hyun Cho ◽  
...  
Keyword(s):  
Atopic Dermatitis ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Opposite Effect ◽  
Egf Receptor ◽  
Skin Lesions ◽  
Epidermal Keratinocytes ◽  
Human Epidermal Keratinocytes ◽  
Epidermal Growth

Atopic dermatitis (AD) is a chronic inflammatory skin disease with a defective immunologic barrier, which is aggravated byStaphylococcus aureus (S. aureus). Epidermal growth factor (EGF) suppresses inflammation and EGF receptor inhibitors increasedS. aureuscolonization. Thus, we investigated the potential roles of EGF in AD, which is often aggravated byS. aureus. We determined how EGF affects the expression of inflammatory cytokines and antimicrobial peptides (AMPs) in human epidermal keratinocytes (HEKs) treated with heat-inactivatedS. aureus(HKSA)in vitroand 2,4-dinitrochlorobenzene-induced AD-like skin lesions in Nc/Nga mice. HKSA increased IL-6 and NFκB expression; EGF treatment had the opposite effect. EGF increased humanβdefensin-2 expression in HEKs and murineβdefensin-3 in mice. In mice, both EGF and pimecrolimus groups showed less erythema with significantly reduced inflammation and decreased expression of thymic stromal lymphopoietin. EGF relievedS. aureus-induced inflammation and AD-like skin lesions in Nc/Nga mice. Therefore, EGF could be a potential topical treatment for AD.

Alterations of ultrastructure and elemental composition in cultured human epidermal keratinocytes after treatment with nitrofurazone and silver sulfadiazine

1987 ◽  
Vol 45 ◽  
pp. 676-677
Author(s):  
A. R. Crooker ◽  
M. C. Myers ◽  
T. L. Beard ◽  
E. S. Graham
Keyword(s):  
Electron Microscopy ◽  
Elemental Composition ◽  
Pyrolytic Carbon ◽  
Human Keratinocytes ◽  
Silver Sulfadiazine ◽  
Epidermal Keratinocytes ◽  
Human Epidermal Keratinocytes ◽  
Culture Systems ◽  
Cytotoxicity Endpoints

Cell culture systems have become increasingly popular as a means of screening toxic agents and studying toxic mechanisms of drugs and other chemicals at the cellular and subcellular levels. These in vitro tests can be conducted rapidly in a broad range of relevant mammalian culture systems; a variety of biological and biochemical cytotoxicity endpoints can be examined. The following study utilized human keratinocytes to evaluate the relative cytotoxicities of nitrofurazone (NF) and silver sulfadiazine (SS), the active ingredients of FURACIN(R) Topical Cream and SILVADENE(R) Cream, respectively. These compounds are anti-infectives used in the treatment of burn patients. Cell ultrastructure and elemental composition were utilized as cytotoxicity endpoints.Normal Human Epidermal Keratinocytes (HK) were prepared from the EpiPackTM culture system (Clonetics Corporation, Boulder, CO). For scanning electron microscopy (SEM) and transmission electron microscopy (TEM), cells were seeded on sterile 35 mm Falcon plastic dishes; for elemental microanalysis, cells were plated on polished pyrolytic carbon discs (E. Fullam, Latham, NY) placed in the culture dishes.

scholarly journals Antioxidant and Pro-Oxidant Capacities as Mechanisms of Photoprotection of Olive Polyphenols on UVA-Damaged Human Keratinocytes

Molecules ◽  
2021 ◽  
Vol 26 (8) ◽  
pp. 2153
Author(s):  
Raffaella Marina Lecci ◽  
Isabella D’Antuono ◽  
Angela Cardinali ◽  
Antonella Garbetta ◽  
Vito Linsalata ◽  
...  
Keyword(s):  
Antioxidant Activities ◽  
Biological Activities ◽  
Human Keratinocytes ◽  
Ldl Oxidation ◽  
Trolox Equivalent Antioxidant Capacity ◽  
Epidermal Keratinocytes ◽  
Olive Cultivar ◽  
Human Epidermal Keratinocytes ◽  
Apoptotic Effect

A wide variety of polyphenols are reported to have considerable antioxidant and skin photoprotective effects, although the mechanisms of action are not fully known. Environmentally friendly and inexpensive sources of natural bioactive compounds, such as olive mill wastewater (OMWW), the by-product of olive-oil processing, can be considered an economic source of bioactive polyphenols, with a range of biological activities, useful as chemotherapeutic or cosmeceutical agents. Green strategies, such as the process based on membrane technologies, allow to recover active polyphenols from this complex matrix. This study aims to evaluate the antioxidant, pro-oxidant, and photoprotective effects, including the underlying action mechanism(s), of the ultra-filtered (UF) OMWW fractions, in order to substantiate their use as natural cosmeceutical ingredient. Six chemically characterized UF-OMWW fractions, from Italian and Greek olive cultivar processing, were investigated for their antioxidant activities, measured by Trolox Equivalent Antioxidant Capacity (TEAC), LDL oxidation inhibition, and ROS-quenching ability in UVA-irradiated HEKa (Human Epidermal Keratinocytes adult) cultures. The photoprotective properties of UF-OMWW were assayed as a pro-oxidant-mediated pro-apoptotic effect on the UVA-damaged HEKa cells, which can be potentially involved in the carcinogenesis process. All the UF-OMWW fractions exerted an effective antioxidant activity in vitro and in cells when administered together with UV-radiation on HEKa. A pro-oxidative and pro-apoptotic effect on the UVA-damaged HEKa cells were observed, suggesting some protective actions of polyphenol fraction on keratinocyte cell cultures.

scholarly journals 5-Aminolevulinic Acid-Based Photodynamic Therapy Pretreatment Mitigates Ultraviolet A-Induced Oxidative Photodamage

2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Hui Hua ◽  
Jiawei Cheng ◽  
Wenbo Bu ◽  
Juan Liu ◽  
Weiwei Ma ◽  
...  
Keyword(s):  
Aminolevulinic Acid ◽  
Epidermal Keratinocytes ◽  
Control Group ◽  
Hacat Cells ◽  
Ultraviolet A ◽  
Hairless Mice ◽  
Human Epidermal Keratinocytes ◽  
Experimental Group

Aim. To determine whether 5-aminolevulinic acid-based photodynamic therapy (ALA-PDT) is effective in combating ultraviolet A- (UVA-) induced oxidative photodamage of hairless mice skin in vivo and human epidermal keratinocytes in vitro. Methods. In in vitro experiments, the human keratinocyte cell line (HaCaT cells) was divided into two groups: the experimental group was treated with ALA-PDT and the control group was left untreated. Then, the experimental group and the control group of cells were exposed to 10 J/m2 of UVA radiation. ROS, O2− species, and MMP were determined by fluorescence microscopy; p53, OGG1, and XPC were determined by Western blot analysis; apoptosis was determined by flow cytometry; and 8-oxo-dG was determined by immunofluorescence. Moreover, HaCaT cells were also treated with ALA-PDT. Then, SOD1 and SOD2 were examined by Western blot analysis. In in vivo experiments, the dorsal skin of hairless mice was treated with ALA-PDT or saline-PDT, and then, they were exposed to 20 J/m2 UVA light. The compound 8-oxo-dG was detected by immunofluorescence. Conclusion. In human epidermal keratinocytes and hairless mice skin, UVA-induced oxidative damage can be prevented effectively with ALA-PDT pretreatment.

Proliferation of K19+ human epidermal keratinocytes in vitro

2007 ◽  
Vol 416 (1) ◽  
pp. 406-408 ◽  
Author(s):  
E. S. Chermnykh ◽  
E. A. Vorotelyak ◽  
S. B. Tkachenko ◽  
A. V. Vasil’ev ◽  
V. V. Terskikh
Keyword(s):  
Epidermal Keratinocytes ◽  
Human Epidermal Keratinocytes

scholarly journals Persea americanaMill. Seed: Fractionation, Characterization, and Effects on Human Keratinocytes and Fibroblasts

2013 ◽  
Vol 2013 ◽  
pp. 1-12 ◽  
Author(s):  
Maria del R. Ramos-Jerz ◽  
Socorro Villanueva ◽  
Gerold Jerz ◽  
Peter Winterhalter ◽  
Alexandra M. Deters
Keyword(s):  
Chlorogenic Acid ◽  
Dermal Fibroblasts ◽  
Persea Americana ◽  
Epidermal Keratinocytes ◽  
Hacat Keratinocytes ◽  
Human Epidermal Keratinocytes ◽  
Residual Solvent ◽  
Keratinocyte Proliferation ◽  
Normal Human

Methanolic avocado (Persea americanaMill., Lauraceae) seed extracts were separated by preparative HSCCC. Partition and HSCCC fractions were principally characterized by LC-ESI-MS/MS analysis. Theirin vitroinfluence was investigated on proliferation, differentiation, cell viability, and gene expression on HaCaT and normal human epidermal keratinocytes (NHEK) and normal human dermal fibroblasts (NHDF). The methanol-water partition (M) from avocado seeds and HSCCC fraction 3 (M.3) were mostly composed of chlorogenic acid and its isomers. Both reduced NHDF but enhanced HaCaT keratinocytes proliferation. HSCCC fractionM.2composed of quinic acid among chlorogenic acid and its isomers inhibited proliferation and directly induced differentiation of keratinocytes as observed on gene and protein level. Furthermore,M.2increased NHDF proliferation via upregulation of growth factor receptors. Salidrosides and ABA derivatives present in HSCCC fractionM.6increased NHDF and keratinocyte proliferation that resulted in differentiation. The residual solvent fractionM.7contained among low concentrations of ABA derivatives high amounts of proanthocyanidins B1 and B2 as well as an A-type trimer and stimulated proliferation of normal cells and inhibited the proliferation of immortalized HaCaT keratinocytes.

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