- Klíčová slova
- terra firma-forme dermatosis,
- MeSH
- 2-propanol terapeutické užití MeSH
- hyperpigmentace etiologie klasifikace patologie MeSH
- keratinocyty patologie MeSH
- keratóza patologie MeSH
- kožní nemoci * diagnóza klasifikace MeSH
- lidé MeSH
- mladiství MeSH
- Check Tag
- lidé MeSH
- mladiství MeSH
- ženské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
Dermal fibroblasts seem critical for epidermal maturation and differentiation and recent work demonstrated that diseased fibroblasts may drive pathophysiological processes. Nevertheless, still very little is known about the actual crosstalk between epidermal keratinocytes and dermal fibroblasts and the impact of dermal fibroblasts on epidermal maturation and differentiation. Aiming for a more fundamental understanding of the impact of the cellular crosstalk between keratinocytes and fibroblasts on the skin homeostasis, we generated full-thickness skin equivalents with and without fibroblasts and subsequently analysed them for the expression of skin differentiation markers, their barrier function, skin lipid content and epidermal cell signalling. Skin equivalents without fibroblasts consistently showed an impaired differentiation and dysregulated expression of skin barrier and tight junction proteins, increased skin permeability, and a decreased skin lipid/protein ratio. Most interestingly, impaired Ras/Raf/ERK/MEK signalling was evident in skin equivalents without fibroblasts. Our data clearly indicate that the epidermal-dermal crosstalk between keratinocytes and fibroblasts is critical for adequate skin differentiation and that fibroblasts orchestrate epidermal differentiation processes.
- MeSH
- buněčná diferenciace MeSH
- epidermální buňky metabolismus patologie MeSH
- epidermis metabolismus MeSH
- fibroblasty metabolismus MeSH
- homeostáza genetika fyziologie MeSH
- keratinocyty metabolismus patologie MeSH
- kožní absorpce MeSH
- kůže metabolismus patologie MeSH
- lidé MeSH
- permeabilita MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Epidermal growth factor receptor (EGFR)-targeted anticancer therapy induces stigmatizing skin toxicities affecting patients' quality of life and therapy adherence. The lack of mechanistic details underlying these adverse events hampers their management. We found that EGFR/ERK signaling is required in LRIG1-positive stem cells during de novo hair eruption to secure barrier integrity and prevent the invasion of commensal microbiota and inflammatory skin disease. EGFR-deficient epidermis is permissive for microbiota outgrowth and displays an atopic-like TH2-dominated signature. The opening of the follicular ostia during hair eruption allows invasion of commensal microbiota into the hair follicle, initiating an additional TH1 and TH17 response culminating in chronic folliculitis. Restoration of epidermal ERK signaling via prophylactic FGF7 treatment or transgenic SOS expression rescues the barrier defect in the absence of EGFR, highlighting a therapeutic anchor point. These data reveal that commensal skin microbiota provoke atopic-like inflammatory skin diseases by invading into the follicular opening of erupting hair.
- MeSH
- antitumorózní látky škodlivé účinky MeSH
- epidermis patologie MeSH
- erbB receptory antagonisté a inhibitory nedostatek MeSH
- fibroblastový růstový faktor 7 metabolismus MeSH
- keratinocyty patologie MeSH
- kůže mikrobiologie patologie MeSH
- lidé MeSH
- MAP kinasový signální systém MeSH
- membránové glykoproteiny metabolismus MeSH
- mikrobiota * MeSH
- myši MeSH
- proteiny nervové tkáně metabolismus MeSH
- vlasy, chlupy patologie MeSH
- zánět patologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Klíčová slova
- adsorpční kolona, TheraSorb Life 18,
- MeSH
- atopická dermatitida * patologie terapie MeSH
- cytokiny fyziologie klasifikace MeSH
- dítě MeSH
- dospělí MeSH
- imunoglobulin E krev MeSH
- imunosorpční techniky * přístrojové vybavení MeSH
- Jobův syndrom patologie MeSH
- keratinocyty patologie MeSH
- kvalita života MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- plazmaferéza * klasifikace metody přístrojové vybavení MeSH
- Th2 buňky MeSH
- výsledek terapie MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
Melanoma represents a malignant disease with steadily increasing incidence. UV-irradiation is a recognized key factor in melanoma initiation. Therefore, the efficient prevention of UV tissue damage bears a critical potential for melanoma prevention. In this study, we tested the effect of UV irradiation of normal keratinocytes and their consequent interaction with normal and cancer-associated fibroblasts isolated from melanoma, respectively. Using this model of UV influenced microenvironment, we measured melanoma cell migration in 3-D collagen gels. These interactions were studied using DNA microarray technology, immunofluorescence staining, single cell electrophoresis assay, viability (dead/life) cell detection methods, and migration analysis. We observed that three 10 mJ/cm2 fractions at equal intervals over 72 h applied on keratinocytes lead to a 50% increase (p < 0.05) in in vitro invasion of melanoma cells. The introduction cancer-associated fibroblasts to such model further significantly stimulated melanoma cells in vitro invasiveness to a higher extent than normal fibroblasts. A panel of candidate gene products responsible for facilitation of melanoma cells invasion was defined with emphasis on IL-6, IL-8, and CXCL-1. In conclusion, this study demonstrates a synergistic effect between cancer microenvironment and UV irradiation in melanoma invasiveness under in vitro condition.
- MeSH
- fibroblasty cytologie patologie MeSH
- imunohistochemie MeSH
- invazivní růst nádoru * MeSH
- keratinocyty patologie účinky záření MeSH
- kokultivační techniky MeSH
- kultivované buňky MeSH
- lidé MeSH
- melanom patologie MeSH
- ultrafialové záření * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: We present herein a series of 14 lesions showing overlapping features with the newly defined benign cutaneous mesenchymal neoplasm labeled as fibroblastic connective tissue nevus (FCTN). METHODS AND RESULTS: Total of 8 patients were male and 5 were female, ranging in age from 1 to 56 years. Lesions appeared as isolated nodules or plaques on the trunk (7 cases), the limbs (4 cases) and the neck (2 cases). Histologically, all cases were composed of bundles of bland spindle cells of fibroblastic/myofibroblastic lineage irregularly branching within the reticular dermis and along fibrous septa in the subcutis. Adnexal structures and dermal adipocytes were entrapped by the fascicles, the epidermis was often papillomatous and elastic fibers were decreased and fragmented. Expression of CD34 and ASMA was found in 8 and 7 cases, respectively. Follow-up was available for 7 patients (mean follow-up, 5 years; range, 1-10 years). None of the cases metastasized or recurred, even when incompletely excised. CONCLUSION: The differential diagnosis of FCTN is broad and includes hypertrophic scar, dermatofibroma, dermatomyofibroma, pilar leiomyoma, plaque-stage DFSP, CD34-positive plaque-like dermal fibroma, fibroblastic-predominant plexiform fibrohistiocytic tumor, lipofibromatosis, superficial desmoid fibromatosis and fibrous hamartoma of infancy, of which it represents probably the monophasic variant.
- MeSH
- antigeny CD34 metabolismus MeSH
- dítě MeSH
- dospělí MeSH
- intradermální névus * metabolismus patologie MeSH
- keratinocyty metabolismus patologie MeSH
- kojenec MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- myofibroblasty * metabolismus patologie MeSH
- nádorové proteiny metabolismus MeSH
- nádory kůže * metabolismus patologie MeSH
- předškolní dítě MeSH
- škára * metabolismus patologie MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- kojenec MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mužské pohlaví MeSH
- předškolní dítě MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
Porokeratózy představují heterogenní skupinu onemocnění, jejichž společným rysem je shodný histopatologický obraz charakterizovaný přítomností tzv. kornoidní lamely. V současnosti je známo 7 nejčastějších klinických variant. Etiologie porokeratóz dosud úplně objasněna nebyla. Kromě genetické predispozice se na vzniku PK zřejmě podílí í zevní faktory. Doporučené léčebné postupy pro léčbu PK dosud nebyly vypracovány, neboť účinnost jednotlivých přípravků či jejich kombinací byla popsána pouze na jednotlivých pacientech, či malých souborech, a kontrolované klinické studie chybí. Autorky poskytují přehled současných znalostí o těchto onemocněních.
Porokeratoses represent a heterogeneous group of diseases which have in common the same histopathologic feature – the presence of cornoid lamela. Currently, there are seven the most frequent clinical variants. The etiology of porokeratoses has not been fully elucidated yet. Combination of genetic predisposition and enviromental factors are playing role in the occurence of porokeratosis. Guidelines for the treatment of porokeratosis have not been drawn up yet as the efficacy of the individual drugs or their combinations have been reported only in individual cases or small case series and controlled clinical studies are lacking. The authors give an overview of the current knowledge on porokeratosis.
- Klíčová slova
- kornoidní lamela,
- MeSH
- dermatoskopie metody MeSH
- diferenciální diagnóza MeSH
- genetická predispozice k nemoci etiologie MeSH
- keratinocyty patologie MeSH
- lidé MeSH
- porokeratóza * diagnóza klasifikace terapie MeSH
- vystavení vlivu životního prostředí MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
Biomedical application of silver nanoparticles (AgNPs) has been rapidly increasing. Owing to their strong antimicrobial activity, AgNPs are used in dermatology in the treatment of wounds and burns. However, recent evidence for their cytotoxicity gives rise to safety concerns. This study was undertaken as a part of an ongoing programme in our laboratory to develop a topical agent for wound healing. Here, we investigated the potential toxicity of AgNPs using normal human dermal fibroblasts (NHDF) and normal human epidermal keratinocytes (NHEK) with the aim of comparing the effects of AgNPs and ionic silver (Ag-I). Besides the effect of AgNPs and Ag-I on cell viability, the inflammatory response and DNA damage in AgNPs and Ag-I-treated cells were examined. The results showed that Ag-I were significantly more toxic than AgNPs both on NHDF and NHEK. Non-cytotoxic concentrations of AgNPs and Ag-I did not induce DNA strand breaks and did not affect inflammatory markers, except for a transient increase in interleukin 6 levels in Ag-I-treated NHDF. The results showed that AgNPs are more suitable for the intended application as a topical agent for wound healing up to the concentration 25 µg/mL.
- MeSH
- antiinfekční látky chemie toxicita MeSH
- buněčné kultury MeSH
- epidermis účinky léků patologie MeSH
- fibroblasty účinky léků patologie MeSH
- keratinocyty účinky léků patologie MeSH
- kovové nanočástice chemie toxicita MeSH
- kultivované buňky MeSH
- kůže účinky léků patologie MeSH
- lidé MeSH
- poškození DNA MeSH
- povrchové vlastnosti MeSH
- stříbro chemie toxicita MeSH
- transmisní elektronová mikroskopie MeSH
- viabilita buněk účinky léků MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Estrogen deprivation is considered responsible for many age-related processes, including poor wound healing. Guided by previous observations that estradiol accelerates re‑epithelialization through estrogen receptor (ER)‑β, in the present study, we examined whether selective ER agonists [4,4',4''-(4-propyl [1H] pyrazole-1,3,5-triyl)‑trisphenol (PPT), ER‑α agonist; 2,3-bis(4-hydroxyphenyl)-propionitrile (DPN), ER‑β agonist] affect the expression of basic proliferation and differentiation markers (Ki‑67, keratin‑10, ‑14 and ‑19, galectin‑1 and Sox‑2) of keratinocytes using HaCaT cells. In parallel, ovariectomized rats were treated daily with an ER modulator, and wound tissue was removed 21 days after wounding and routinely processed for basic histological analysis. Our results revealed that the HaCaT keratinocytes expressed both ER‑α and ‑β, and thus are well-suited for studying the effects of ER agonists on epidermal regeneration. The activation of ER‑α produced a protein expression pattern similar to that observed in the control culture, with a moderate expression of Ki‑67 being observed. However, the activation of ER‑β led to an increase in cell proliferation and keratin‑19 expression, as well as a decrease in galectin‑1 expression. Fittingly, in rat wounds treated with the ER‑β agonist (DPN), epidermal regeneration was accelerated. In the present study, we provide information on the mechanisms through which estrogens affect the expression patterns of selected markers, thus modulating keratinocyte proliferation and differentiation; in addition, we demonstrate that the pharmacological activation of ER-α and -β has a direct impact on wound healing.
- MeSH
- alfa receptor estrogenů agonisté metabolismus MeSH
- beta receptor estrogenů agonisté metabolismus MeSH
- buněčná diferenciace účinky léků MeSH
- buněčné linie MeSH
- fenoly farmakologie MeSH
- hojení ran účinky léků MeSH
- keratinocyty cytologie účinky léků metabolismus patologie MeSH
- kůže účinky léků metabolismus patologie MeSH
- lidé MeSH
- nitrily farmakologie MeSH
- potkani Sprague-Dawley MeSH
- pyrazoly farmakologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH