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 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.

scholarly journals Gps2, a Protein Partner for Human Papillomavirus E6 Proteins

2001 ◽  
Vol 75 (1) ◽  
pp. 151-160 ◽  
Author(s):  
Yan Yan Degenhardt ◽  
Saul J. Silverstein
Keyword(s):  
Transcriptional Activation ◽  
Epidermal Keratinocytes ◽  
Human Epidermal Keratinocytes ◽  
Papilloma Virus ◽  
Hpv E6 ◽  
Yeast Two Hybrid System ◽  
Protein Partners ◽  
Normal Human

ABSTRACT We have used the yeast two-hybrid system to screen a cDNA library prepared from normal human epidermal keratinocytes and identified protein partners for human papilloma virus (HPV) E6 proteins. A clone that encoded Gps2 interacted with E6 proteins from HPVs of high and low oncogenic risk. The specificity of these reactions was verified and the regions of E6 that were required for interaction were mapped. Steady-state and pulse-chase analyses of cells cotransfected with DNAs expressing E6 from either HPV6 or HPV18 and Gps2 demonstrated that the E6 proteins induced the degradation of Gps2 in vivo but not in vitro. Gps2 exhibited transcriptional activation activity, and high-risk E6 suppressed this activity.

Apoptosis is not required for acantholysis in pemphigus vulgaris

2009 ◽  
Vol 296 (1) ◽  
pp. C162-C172 ◽  
Author(s):  
Enno Schmidt ◽  
Judith Gutberlet ◽  
Daniela Siegmund ◽  
Daniela Berg ◽  
Harald Wajant ◽  
...  
Keyword(s):  
Caspase 3 ◽  
Pemphigus Vulgaris ◽  
Human Keratinocytes ◽  
Skin Lesions ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Epidermal Keratinocytes ◽  
Death Domain ◽  
Human Epidermal Keratinocytes ◽  
Desmosomal Cadherins ◽  
Normal Human

The autoimmune blistering skin disease pemphigus vulgaris (PV) is caused primarily by autoantibodies against desmosomal cadherins. It was reported that apoptosis can be detected in pemphigus skin lesions and that apoptosis can be induced by PV-IgG in cultured keratinocytes. However, the role of apoptosis in PV pathogenesis is unclear at present. In this study, we provide evidence that apoptosis is not required for acantholysis in PV. In skin lesions from two PV patients, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) positivity, but not cleaved caspase-3, was detected in single keratinocytes in some lesions but was completely absent in other lesions from the same patients. In cultures of human keratinocytes (HaCaT and normal human epidermal keratinocytes), PV-IgG from three different PV patients caused acantholysis, fragmented staining of Dsg 3 staining, and cytokeratin retraction in the absence of nuclear fragmentation, TUNEL positivity, and caspase-3 cleavage and hence in the absence of detectable apoptosis. To further rule out the contribution of apoptotic mechanisms, we used two different approaches that are effective to block apoptosis induced by various stimuli. Inhibition of caspases by z-VAD-fmk as well as overexpression of Fas-associated death domain-like interleukin-1β-converting enzyme (FLICE)-like inhibitory proteins FLIPL and FLIPS to inhibit receptor-mediated apoptosis did not block PV-IgG-induced effects, indicating that apoptosis was not required. Taken together, we conclude that apoptosis is not a prerequisite for skin blistering in PV but may occur secondary to acantholysis.

scholarly journals Nuclear Factor-κB Binds to the Epstein-Barr Virus LMP1 Promoter and Upregulates Its Expression

2008 ◽  
Vol 83 (3) ◽  
pp. 1393-1401 ◽  
Author(s):  
Pegah Johansson ◽  
Ann Jansson ◽  
Ulla Rüetschi ◽  
Lars Rymo
Keyword(s):  
B Cells ◽  
Epstein Barr Virus ◽  
Affinity Purification ◽  
Critical Role ◽  
Mobility Shift ◽  
Barr Virus ◽  
Exogenous Expression ◽  
Epstein Barr

ABSTRACT The latent membrane protein 1 (LMP1) oncogene carried by Epstein-Barr virus (EBV) is essential for transformation and maintenance of EBV-immortalized B cells in vitro, and it is expressed in most EBV-associated tumor types. The activation of the NF-κB pathway by LMP1 plays a critical role in the upregulation of antiapoptotic proteins. The EBV-encoded EBNA2 transactivator is required for LMP1 activation in latency III, while LMP1 itself appears to be critical for its activation in the latency II gene expression program. In both cases, additional viral and cellular transcription factors are required in mediating transcription activation of the LMP1 promoter. Using DNA affinity purification and chromatin immunoprecipitation assay, we showed here that members of the NF-κB transcription factor family bound to the LMP1 promoter in vitro and in vivo. Electrophoretic mobility shift assay analyses indicated the binding of the p50-p50 homodimer and the p65-p50 heterodimer to an NF-κB site in the LMP1 promoter. Transient transfections and reporter assays showed that the LMP1 promoter is activated by exogenous expression of NF-κB factors in both B cells and epithelial cells. Exogenous expression of NF-κB factors in the EBNA2-deficient P3HR1 cell line induced LMP1 protein expression. Overall, our data are consistent with the presence of a positive regulatory circuit between NF-κB activation and LMP1 expression.

In vitro cellular immunity to epstein-barr virus in normal human subjects

1974 ◽  
Vol 13 (5) ◽  
pp. 599-605 ◽  
Author(s):  
Peter J. Fimmel ◽  
Patrick K. Lai ◽  
David Keast ◽  
Michael P. Alpers ◽  
Ewart M. Mackay-Scollay
Keyword(s):  
Cellular Immunity ◽  
Epstein Barr Virus ◽  
Human Subjects ◽  
Barr Virus ◽  
Normal Human ◽  
Epstein Barr

scholarly journals N-Succinyl-S-Farnesyl-L-Cysteine (SFC): A Novel Isoprenylcysteine Analog with In Vitro Anti-Inflammatory Activity and Clinical Skin Protecting Properties

Cosmetics ◽  
2021 ◽  
Vol 8 (4) ◽  
pp. 110
Author(s):  
José R. Fernández ◽  
Karl Rouzard ◽  
Corey Fitzgerald ◽  
Jason Healy ◽  
Masanori Tamura ◽  
...  
Keyword(s):  
Small Molecule ◽  
Dermal Fibroblasts ◽  
Epidermal Keratinocytes ◽  
Double Blind ◽  
Human Epidermal Keratinocytes ◽  
New Class ◽  
Normal Human ◽  
Anti Inflammatory ◽  
Split Face

Over the past 15 years, small molecule isoprenylcysteine (IPC) analogs have been identified as a potential new class of topical anti-inflammatories. Clinical studies have demonstrated that IPCs are both safe and effective in promoting healthy skin when applied topically. This work aims to demonstrate N-Succinyl-S-farnesyl-L-cysteine (SFC) as a novel IPC molecule that provides a broad spectrum of benefits for skin. Human promyelocytic cell line HL-60, human dermal microvascular endothelial cells (HDMECs), human dermal fibroblasts (HDFs), and normal human epidermal keratinocytes (NHEKs) were exposed in culture to various inducers to trigger reactive oxygen species, cytokines, or collagenase production. A 49-subject randomized double-blind, vehicle-controlled, split face trial was performed with 1% SFC gel, or 5% niacinamide and vehicle applied for 12 weeks to evaluate anti-wrinkle and anti-aging endpoints. We demonstrated that SFC inhibited GPCR and TLR-induced pro-inflammatory cytokine release in NHEKs and HDMECs from several inflammatory inducers such as UVB, chemicals, cathelicidin, and bacteria. SFC successfully reduced GPCR-induced oxidation in differentiated neutrophils. Moreover, photoaging studies showed that SFC reduced UVA-induced collagenase (pro-MMP-1) production in HDFs. Clinical assessment of 1% SFC gel demonstrated improvement above the vehicle for wrinkle reduction, hydration, texture, and overall appearance of skin. N-Succinyl-S-farnesyl-L-cysteine (SFC) is a novel anti-inflammatory small molecule and is the first farnesyl-cysteine IPC shown to clinically improve appearance and signs of aging, while also having the potential to ameliorate inflammatory skin disorders.

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.

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