bromochloroacetic-acid and Sunburn

Topics: Androgens; Animals; Autoradiography; Carbon Dioxide; Cell Differentiation; Cytoplasmic Granules; Humans; Keratins; Kinetics; Melanins; Melanocytes; Microcirculation; Mitosis; Regional Blood Flow; Sebaceous Glands; Sebum; Skin; Skin Absorption; Skin Physiological Phenomena; Sunburn; Ultraviolet Rays

For ethical and technical reasons, the in vivo biological effects of ultraviolet (UV) radiation on skin are difficult to study in human volunteers. The use of human skin grafted on to nude mice may circumvent this difficulty.. To investigate the effects of a single moderate UVB exposure on human skin grafted on to nude mice.. Modifications of epidermal differentiation markers and patterns of keratin expression were assessed from 24 h to 14 days after a physiological UVB irradiation characterized by the induction of sunburn cells.. During the first 48 h postexposure, involucrin, loricrin, transglutaminase type I, filaggrin and keratin K2e expression were altered together with the formation of abnormal horny layers. Constitutive keratin K14 was increased while keratin K10 expression was delayed. Newly synthesized keratins K6, K16, K17 and K19 were induced in parallel with an increase in the epidermal proliferation rate. A progressive normalization of both keratinocyte proliferation and differentiation took place during the following days, reaching completion within 2 weeks.. Exposure of human skin to a UVB dose corresponding to a mild sunburn reaction induces epidermal hyperproliferation and alterations of several constitutive differentiation markers, as well as a drastic modification in the pattern of epidermal keratins. Although these modifications were shown to be progressively reversed in a single exposure model, the data also suggest that subsequent UV exposures occurring during the recovery period may lead to potentially deleterious long-term consequences, such as photoageing and photocarcinogenesis. Grafted human skin appeared to be an attractive and promising model for investigating the biological consequences of UVB radiation in vivo.

Topics: Animals; Biomarkers; Cell Differentiation; Cell Division; Dose-Response Relationship, Radiation; Filaggrin Proteins; Humans; Intermediate Filament Proteins; Keratinocytes; Keratins; Membrane Proteins; Mice; Mice, Nude; Protein Precursors; Radiation Injuries; Skin; Skin Transplantation; Sunburn; Transglutaminases; Transplantation, Heterologous; Ultraviolet Rays

Hair follicle (HF) growth and regression is an exquisitely regulated process of cell proliferation followed by massive cell death and is accompanied by cyclical expression of the apoptosis regulatory gene pair, Bcl-2 and Bax. To further investigate the role of Bcl-2 expression in the control of hair growth and keratinocyte apoptosis, we have used transgenic mice that overexpress human Bcl-2 in basal epidermis and in the outer root sheath under the control of the human keratin-14 promoter (K14/Bcl-2). When irradiated with ultraviolet B (UVB) light, K14/Bcl-2 mice developed about 5-10-fold fewer sunburn cells (ie, apoptotic keratinocytes) in the basal layer of the epidermis, compared to wild-type mice, whereas cultures of primary keratinocytes from transgenic mice were completely resistant to UVB-induced histone formation, at doses that readily induced histone release from wild-type cells. K14/Bcl-2 mice show no alteration of neonatal hair follicle morphogenesis or of the onset of the first wave of HF regression (catagen). However, compared to wild-type controls, K14/Bcl-2 mice subsequently displayed a significant acceleration of spontaneous catagen progression. During chemotherapy-induced alopecia, follicular dystrophy was promoted in K14/Bcl-2 mice. Thus, although K14-driven overexpression of Bcl-2 protected murine epidermal keratinocytes from UVB-induced apoptosis, it surprisingly promoted catagen- and chemotherapy-associated keratinocyte apoptosis.

Topics: Alopecia; Animals; Antineoplastic Agents; Antineoplastic Agents, Alkylating; Apoptosis; Cyclophosphamide; Epidermis; Gene Expression; Hair Follicle; Humans; Keratin-14; Keratinocytes; Keratins; Mice; Mice, Inbred Strains; Mice, Transgenic; Phenotype; Proto-Oncogene Proteins c-bcl-2; Reference Values; Skin; Sunburn; Transgenes; Ultraviolet Rays

Topics: Age Factors; Aged; Dilatation, Pathologic; Elastic Tissue; Hair Follicle; Humans; Keratins; Male; Middle Aged; Rhinophyma; Sebaceous Glands; Sebum; Sex Factors; Skin Aging; Sunburn

Sunburn cells (SBCs) appear in the epidermis shortly after acute UV damage, especially after exposure to UVB light. As yet, the mode of their formation remains to be satisfactorily elucidated. In order to characterize these cells, the expression of various markers of epidermal differentiation following UV exposure was investigated using immunhistochemical procedures. These were applied to paraffin-embedded (microwave technique) and frozen specimens of human skin 24 h after irradiation with 4 times the minimal erythema doses(MED). Normal nonirradiated skin without irradiation served as the control. We used a battery of antibodies directed against the following: cytokeratins (CKs) 5, 10, 17, and 19, actin, cell-adhesion proteins (desmoplakins, desmogleins), markers of terminal epidermal differentiation (filaggrin, involucrin and loricrin), markers of proliferation (PCNA, MIB, K6,16), a marker of endocytosis (clathrin) and markers of cell growth, (transforming growth factor [TGF-alpha]) and B-cell leukemia/lymphoma-2 [bcl-2]. After UV irradiation it was found that CK 5, which is typically confined to basal keratinocytes, was also expressed in suprabasal keratinocytes. The CKs 1 and 10/11 exhibit a normal suprabasal localization, but suprisingly, SBCs were negative for these CKs. Although CK 6,16, and 17 are not usually found in normal epidermis, UVB exposure induced their expression in suprabasal keratinocytes, but again failed to elicit their expression in SBCs. Antibodies specific for markers of late epidermal differentiation (filaggrin, involucrin and loricrin), cell-junction proteins (desmogleins, desmoplakins), proliferation (PCNA and MIB), and endocytosis (clathrin) also failed to produce positive staining of SBCs. Even though TGF-alpha immunoreactivity became detectable in most keratinocytes after UV exposure, this was not the case for SBCs. The number of basally located dendritic cells, most probably melanocytes, exhibiting bcl-2 staining was markedly reduced 6 and 12 h after irradiation as compared with normal skin. SBCs do not express any late differentiation markers, but they do contain proteins typical of basal keratinocytes (CK 5). It can be concluded that SBCs do not develop beyond a more basal-like differentiation pattern, probably as a result of cell death and migration through the epidermis.

Topics: Actins; Antigens, Nuclear; Biomarkers; Cell Adhesion Molecules; Cell Differentiation; Cell Division; Clathrin; Cytoskeletal Proteins; Dendritic Cells; Desmogleins; Desmoplakins; Endocytosis; Epidermis; Filaggrin Proteins; Gene Expression Regulation; GTP-Binding Proteins; Humans; Intermediate Filament Proteins; Keratinocytes; Keratins; Melanocytes; Membrane Proteins; Nuclear Proteins; Proliferating Cell Nuclear Antigen; Protein Precursors; Protein-Tyrosine Kinases; Proto-Oncogene Proteins c-bcl-2; Sunburn; Tumor Necrosis Factor-alpha; Ultraviolet Rays

While some cutaneous squamous cell carcinomas (SCC) arise from predisposing conditions such as burn scars, draining sinuses, and chronic, nonhealing wounds, the vast majority of these tumors arise from actinically damaged epidermis. It has been shown previously that keratinocytes within healing wounds show an "activated" immunophenotype when stained with antibodies to psi-3, involucrin, filaggrin, and cytokeratins. A similar pattern has been seen in keratinocytes from patients with recessive dystrophic epidermolysis bullosa (RDEB), in whom the incidence of cutaneous SCC is markedly increased. We tested the hypothesis that actinic keratoses (AK), recognized as precursors in the development of the majority of SCC, would show a similar activated immunophenotype when stained with the antibody panel described above. We examined 10 AK, biopsied from the facies and extremities of ten patients, ages 60 to 80, with antibodies to psi-3, involucrin, filaggrin, and AE1. All lesions examined had an immunostaining pattern indistinguishable from that seen in keratinocytes from patients with RDEB or within healing wounds. There was suprabasilar staining of keratinocytes with antibodies to psi-3 and AE1. Involucrin and filaggrin was expressed by all keratinocytes above the midstratum spinosum. Within the acrosyringia and acrotrichia, the staining pattern was that of the normal epidermis, i.e., AE1 staining of basal keratinocytes, granular layer staining of involucrin and filaggrin, and absence of psi-3 expression. These data suggest that an activated keratinocyte phenotype is a unifying feature in conditions which predispose to development of cutaneous SCC.

Topics: Aged; Aged, 80 and over; Antibodies, Monoclonal; Carcinoma, Squamous Cell; Epidermis; Female; Filaggrin Proteins; Humans; Intermediate Filament Proteins; Keratinocytes; Keratins; Keratosis; Male; Middle Aged; Phenotype; Precancerous Conditions; Protein Precursors; Skin Neoplasms; Sunburn

Human keratinocytes in culture were prelabeled with [3H]arachidonic acid (AA) and then exposed to ultraviolet B radiation. Irradiated cells released labeled AA metabolites into media in a dose-dependent manner when compared to sham-irradiated cells. The response began immediately and continued for 24 h. Extracts from media were examined by high-performance liquid chromatography for identification of specific AA metabolites. Irradiated cells were stimulated to produce prostaglandin-like material (PGE2 and PGF2 alpha). These findings support the concept that the cell membrane of keratinocytes participates directly or indirectly in initiating the sunburn response. It is also felt that the metabolites formed following injury to the membrane are an integral component in the mediation of that response.

Topics: Arachidonic Acids; Cell Membrane; Cells, Cultured; Chromatography, High Pressure Liquid; Dinoprost; Dinoprostone; Dose-Response Relationship, Radiation; Epidermis; Humans; Keratins; Photochemistry; Prostaglandins E; Prostaglandins F; Sunburn; Ultraviolet Rays

Topical application of a 2.5 per cent indomethacin (IM) solution to the sunburned skin of humans and guinea pigs resulted in a marked decrease in ultraviolet light (UVL) -induced erythema. In humans, a decrease in skin temperatute and hyperalgesia to near normal levels was also observed. Epidermal responses to UVL injury such as keratinocyte cell death and altered DNA synthesis proceeded unmodified by IM. Repeated applications of IM in the 48-hr period following UVL exposure did not improve upon the results obtained following a single treatment. Guinea-pig skin provides a relevant model system for evaluating the effects of topical nosteroidal anti-inflammatory agents on sunburn.

Topics: Administration, Topical; Animals; Cell Survival; Depression, Chemical; DNA; Erythema; Female; Guinea Pigs; Humans; Hyperalgesia; Indomethacin; Keratins; Prostaglandin Antagonists; Prostaglandins; Radiation Effects; Skin; Skin Temperature; Sunburn; Thymidine; Ultraviolet Rays

Topics: Catechol Oxidase; Cell Nucleus; Cytoplasmic Granules; Desmosomes; Dihydroxyphenylalanine; Endoplasmic Reticulum; Golgi Apparatus; Hair; Histocytochemistry; Humans; Inclusion Bodies; Intercellular Junctions; Keratins; Male; Melanins; Microscopy, Electron; Microtubules; Mitochondria; Pigments, Biological; Sunburn; Ultraviolet Rays

Topics: Cell Nucleus; Cytoplasm; Desmosomes; Humans; Intercellular Junctions; Keratins; Melanins; Skin; Sunburn; Ultraviolet Rays

Topics: Humans; Keratins; Keratosis; Lysosomes; Microscopy, Electron; Skin; Sunburn; Time Factors; Ultraviolet Rays

Topics: Albinism; Black People; Body Temperature; Erythema; Humans; Keratins; Pellagra; Pigmentation; Skin; Sunburn; Ultraviolet Rays