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At least 37 records · Page 2Linked to original sources
PubMed1990

Reconstituted epidermis: a novel model for the study of drug metabolism in human epidermis.

The metabolic capacity of reconstituted epidermis from the outer root sheath cells of human hair follicles was determined. It was found that this epidermis possesses enzymes involved in both phase I (oxidation) and phase II (conjugation) reactions for drug biotransformation. The use of model substrates allowed the characterization of several isoenzymes. The homogenate fraction contained membrane-bound mixed-function oxydases (cytochrome P-450 dependent) involved in the O-dealkylation of 7-ethoxy-, 7-pentoxy-, and 7-benzoxyresorufin, NADPH cytochrome c (P-450) reductase, testosterone 5 alpha-reductase, and UDP-glucuronosyltransferases, which conjugate 1-naphthol and bilirubin. One isoform of each glutathione S-transferase, steroid-, and arylsulfatases, acting on estrone- and 4-methylumbelliferone sulfates, was detected. Additionally, the activity of two distinct forms of epoxide hydrolases, which hydrate cis- and trans-stilbene oxides, could be measured. The presence of these drug metabolizing enzymes in the reconstituted epidermis indicates that it has a potential to serve as a model to study epidermal drug metabolism in vitro.

Arylsulfatases↗
PubMed2004

Suprabasal expression of human amphiregulin in the epidermis of transgenic mice induces a severe, early-onset, psoriasis-like skin pathology: expression of amphiregulin in the basal epidermis is also associated with synovitis.

The expression of amphiregulin (AR) in the basal epidermis of transgenic mice [keratin 14 promoter AR gene (K14-ARGE)] has been previously shown to induce an early-onset and severe skin pathology, with many similarities to psoriasis. In this study, it is demonstrated that involucrin enhancer/promoter-dependent expression of human AR (INV-AR) in the suprabasal epidermis of transgenic mice also produces a cutaneous psoriasis-like phenotype. INV-AR mice possess a limited lifespan and scaling, papillomatous, erythematous skin with partial alopecia. INV-AR mouse histopathology also revealed epidermal hyperkeratosis, parakeratosis, acanthosis, and an exaggerated dermal vasculature. A dermal and epidermal infiltrate was also evident and consisted of both neutrophils and CD3(+) T lymphocytes. The histology of synovial joints in both the INV-AR mice and the K14-ARGE mice of our previous investigation was examined. The histologic examination revealed that 3-week-old INV-AR transgenic mice displayed normal knee joint histology, while 2- to 3-week-old K14-ARGE transgenic mice frequently displayed synovitis, as exemplified by the presence of a mixed leukocytic infiltration, increased vascularization, and enhanced deposition of fibrous matrix in the knee synovium. These results demonstrate that AR overexpression in both the basal and suprabasal epidermis of transgenic mice induces a phenotype that mimics cutaneous psoriasis, while basal AR expression is also associated with synovial inflammation, a precursor to the psoriasis-associated arthropathy, psoriatic arthritis. Collectively, the results implicate epidermal AR expression as a possible mediator of innate cutaneous immunity and epidermal proliferation and also as a potential trigger of both cutaneous psoriasis and psoriatic arthritis.

Age of Onset↗
PubMedDate not supplied

A novel polypeptide p10 expressed in tumor-promoter-treated murine epidermis and in untreated neonatal murine epidermis.

12-O-Tetradecanoyl-phorbol-13-acetate (TPA) has been shown to induce a broad variety of morphological and metabolic changes in mouse skin. These include gross changes in cell growth as well as subtle changes regarding gene expression. Changes in the induction of specific proteins have been described, but it is not yet clear, if there exists a strict causal correlation between the induction of expression of specific proteins and the phenomenon of tumor promotion. At least some of these proteins might also be correlated with an accompanying hyperproliferative effect. This has been shown for protein p10, a 10 kDa protein not found in untreated adult mouse epidermis. The expression of this protein can be induced de novo after the topical administration of TPA. It is also shown, that p10 is expressed in untreated neonatal murine epidermis. Due to the induction of this protein by irritation, hyperproliferation-causing tumor promoters and due to the observable abundance in neonatal epidermis, this protein seems not strictly related to tumor promotion, but rather to proliferation and differentiation.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1975

Prostaglandins and cyclic AMP in epidermis. Evidence for the independent action of prostaglandins and adrenaline on the adenyl cyclase system of pig and human epidermis, normal and psoriatic.

Prostaglandins E1 and E2 stimulate cyclic AMP accumulation in pig epidermis and in human epidermis from patients with psoriasis. Prostaglandins A1,A2 and F2alpha are relatively ineffective. The fact that this stimulation is not inhibited by a beta-blocker (propranolol) and that the stimulation by prostaglandin E2 and adrenaline is additive indicates that each drug acts independently on the epidermal adenyl cyclase system. In other words, prostaglandins E1 and E2 act on a site other than the beta-receptor of adenyl cyclase in epidermis. The stimulation by prostaglandins E1 and E2 is not additive; hence they probably act on the same site. Concentrations of prostaglandin E above 3X10(-7) M are effective in causing stimulation. This concentration may be within the physilogical range and the contribution of endogenous prostaglandin levels in the control of intracellular cyclic AMP levels cannot be disregarded.

Adenylyl Cyclases↗
PubMedDate not supplied

Presence of serum albumin in normal human epidermis: possible implications for the nutrition and physiology of stratified epithelia. Presence of albumin in epidermis.

In this paper, using both immunofluorescence and protein biochemistry techniques, we present definitive evidence that plasma proteins such as albumin are present within normal human epidermis. This result confirms several previous reports supporting the idea that relatively large molecules can diffuse through the epidermal basement membrane into epidermis. Our results bring new insights for discussing how hydrophobic ligands or drugs present in the bloodstream and bound to plasmatic carriers can reach epidermal cells of all layers.

Electrophoresis, Gel, Two-Dimensional↗
PubMed1994

Pemphigus foliaceus autoantibodies bind both epidermis and squamous mucosal epithelium, but tissue injury is detected only in the epidermis. The Cooperative Group on Fogo Selvagem Research.

BACKGROUND: Fogo selvagem (FS) is an autoimmune intraepidermal blistering disease mediated by antidesmosomal autoantibodies. Patients with FS do not have mucosal lesions despite extensive skin involvement. OBJECTIVE: Our purpose was to evaluate the epidermis and the oral epithelium of patients with FS as targets of antidesmosomal autoantibodies. METHODS: Fifteen patients were studied clinically, histologically, and immunologically. Biopsy specimens from the skin and the oral mucosa were studied by light microscopy and direct immunofluorescence. The serum of each of these patients was also titrated by indirect immunofluorescence. RESULTS: All patients showed skin lesions and subcorneal acantholyis, but none exhibited oral blisters or erosions. Direct immunofluorescence analysis demonstrated the presence of tissue-bound autoantibodies in both the epidermis and the oral epithelium of all patients with FS. Antiepidermal autoantibodies were also found in the sera of the patients. CONCLUSION: Relevant epitopes on desmoglein 1 molecules of oral epithelium may not be available to react with pathogenic FS autoantibodies.

Adolescent↗
PubMed1986

Epidermis and lymphocyte interactions during a tuberculin skin reaction. II. Epidermis contains specific lymphocyte chemotactic factors.

Lymphocyte chemotaxis was studied in a blind-well chamber assay by measuring the passage of 51Cr-labeled cells through a polycarbonate filter with a pore size of 5 micron. Monocyte-depleted lymphocytes were divided into T cells (E receptor-positive lymphocytes) and non-T cells. T lymphocytes showed pronounced migration after exposure to leukotriene B4 (LTB4) and casein, and weak migration after exposure to N-formyl-methionyl-leucyl-phenylalanine (FMLP). Non-T cells showed strong migration after exposure to FMLP, but weak migration after exposure to casein and LTB4. Supernatants of homogenized suction blisters from normal skin did not induce active migration. However, if the epidermis came from an area overlying a positive tuberculin skin reaction, there was a significant migration mostly of T, but also of non-T cells. Supernatants from phytohemagglutinin (PHA)-stimulated lymphocyte cultures also contained lymphocyte chemotactic factor(s), which, however, had an effect only on T lymphocytes. Purified protein derivative of tuberculin (PPD)-stimulated lymphocytes did not produce chemoattractants either for T or for non-T cells. These studies show that lymphocytes can show active, directed migration following exposure to well-known chemotaxins for granulocytes and monocytes although their migrational capability differs for different subpopulations. Epidermis overlying a cell-mediated immune reaction (tuberculin) contains epidermal lymphocyte chemotactic factor(s). This factor(s) may be of importance for the type of cell infiltrate occurring in certain dermatologic disorders.

Caseins↗
PubMed1981

Epidermis extracts (chalone) inhibit cell flux at the the G1-S, S-G2 and G2-M transitions in mouse epidermis.

Epidermal cell flux at the G1-S, S-G2 and G2-M transition was examined during the first 4 hr after injection of epidermis extract. The flux parameters were estimated by a combination of several methods. The G1-S and S-G2 transit rates were calculated on the basis of a double labelling technique with [3H]TdR, the G2-M flux by means of colcemid and the relative proportion of cells in the S or G2 phase by means of flow cytometry. All experiments were performed both in early morning and late evening, corresponding to maximum and minimum rates of epidermal cell proliferation in the hairless mouse. The epidermis extract inhibited the S-G2 and G2-M transit rates to the same degree, while the inhibition of cell flux at the G1-S transit was consistently stronger. In general, the inhibition of cell flux at the different transitions was most pronounced when the rate of cell proliferation was low and vice versa.

Animals↗
PubMed2002

Ectopic expression of desmin in the epidermis of transgenic mice permits development of a normal epidermis.

Cell architecture is largely based on the interaction of cytoskeletal proteins, which include intermediate filaments (IF), microfilaments, microtubules, as well as their type-specific membrane-attachment structures and associated proteins. In order to further our understanding of IF proteins and to address the fundamental issue whether different IF perform unique functions in different tissues, we expressed a desmin transgene in the basal epidermis of mice. Ectopic expression of desmin led to the formation of an additional, keratin-independent IF cytoskeleton and did not interfere with the keratin-desmosome interaction. We show that ectopic expression of a type III IF protein in basal keratinocytes did not interfere with the normal epidermal architecture and the program of terminal differentiation. This demonstrated that keratinocytes suffered no obvious detrimental effects from extra desmin filaments in their cytoplasm. In addition, we asked whether stable expression of desmin could rescue K5 null mice, which served as a model for severe EBS. Transgenic mice ectopically expressing desmin in the basal layer were mated with K5 heterozygous deficient animals to generate desmin rescue mice and analysed. In summary, our study support the notion that the different IF like desmin or keratins composing a IF network in vivo are central to cytoskeletal architecture and design in cells.

Animals↗
PubMed1977

Ultrastructural studies of nuclei and nucleoli in psoriatic epidermis, compared with those in normal epidermis.

Quantitative and qualitative differences of the nuclear and nucleolar structures in normal and psoriatic (involved and uninvolved) epidermis were revealed with the electron microscope. The size of nuclei and nucleoli was increased, the frequency of nuclear bodies was increased, and the relative amount of heterochromatin was decreased in involved skin compared to normal or uninvolved skin. There was no significant difference between normal skin and uninvolved skin of psoriasis. In addition to these changes, multiple fibrillar centers within nucleoli and small masses of chromatin in the epidermal nucleoplasm were observed very frequently in involved skin, while rarely or not at all in normal and uninvolved skin. These results suggest that involved psoriatic keratinocytes have increased metabolic activity and abnormal protein synthesis, having undergone gene derepression.

Adolescent↗
PubMed2000

High-pressure freezing provides new information on human epidermis: simultaneous protein antigen and lamellar lipid structure preservation. Study on human epidermis by cryoimmobilization.

Current transmission electron microscopy techniques do not permit simultaneous visualization of skin ultrastructure and stratum corneum extracellular lipids. We developed a new procedure, which entails application of high-pressure freezing followed by freeze-substitution with acetone containing uranyl acetate, followed by low temperature embedding in HM20. Electrospray ionization mass spectrometry showed that the amount of lipids lost during preparation was minimal. The ultrastructure of cryoprocessed skin was compared with that of conventionally prepared skin samples. Cryoprocessing, but not conventional processing, enabled visualization of lipid stacks within epidermal lamellar bodies, as well as the extracellular lipid domains of the stratum corneum and the ultrastructure within keratinocytes. Anti-filaggrin immunocytochemistry also showed, e.g., excellent preservation of filaggrin on cryoprocessed samples. Additionally, the cytosol of keratinocytes appeared to be organized in "microdomain"-like areas. Finally, the stratum corneum appeared more compact with smaller intercellular spaces and hence tighter cell-cell interactions, after cryoprocessing, than after conventional tissue preparation for transmission electron microscopy. We conclude here that only cryoprocessing preserves skin in a close to native state.

Adult↗