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1.
Eur J Dermatol ; 23(5): 663-70, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24135214

RESUMO

OBJECTIVES: As outdoor workers, seafarers have high levels of work-related exposure to UV radiation. Considering the various ethnic shipboard crews, this study aimed to assess the prevalence of UV induced skin ageing symptoms among seafarers and their attitude towards sunlight exposure. METHODS: One dermatologist examined 514 seafarers and documented the presence of 11 extrinsic skin ageing symptoms. Based on a questionnaire, the seafarers' attitudes and sun protection were evaluated. RESULTS: On average, 4 extrinsic skin ageing symptoms were found among the seafarers without significant differences between ethnic groups. Teleangiectasis (n = 381), coarse wrinkles (n = 315) and lentigines solares (n = 228) were the most frequently observed extrinsic symptoms. In the multivariate analysis, the parameters current smoking (OR 1.52 (1.01-2.27)), shipboard rank (deck personnel, galley staff vs. engine room personnel; (OR 1.40 (1.01-1.94)), and age (OR 1.07 (1.05-1.10)) were significantly associated with developing skin ageing symptoms. Only half of the seafarers examined were aware of their elevated risk of photodamage due to their high UV exposure at sea. More non-Caucasian than Caucasian seafarers perceived tanned skin as rather positive (78.0% vs. 52.4%; p = 0.002); however, more Caucasian than non-Caucasian seafarers enjoyed intensive sunbathing (17.0% vs. 14.0%). Furthermore, 55.7% of the seafarers (significantly more often Caucasians) used sunscreens during sunlight exposure at sea. CONCLUSIONS: The various ethnic groups examined differed in their attitude and behaviour towards shipboard sun exposure. Education of shipboard crews is required about possible severe health effects due to sun exposure at sea.


Assuntos
Lentigo/epidemiologia , Exposição Ocupacional/efeitos adversos , Navios , Envelhecimento da Pele , Luz Solar/efeitos adversos , Telangiectasia/epidemiologia , Raios Ultravioleta/efeitos adversos , Adulto , Fatores Etários , Idoso , Estudos Transversais , Eritema/epidemiologia , Eritema/etiologia , Comportamentos Relacionados com a Saúde/etnologia , Conhecimentos, Atitudes e Prática em Saúde/etnologia , Humanos , Lentigo/etiologia , Masculino , Pessoa de Meia-Idade , Medicina Naval , Saúde do Trabalhador , Prevalência , Fatores de Risco , Envelhecimento da Pele/etnologia , Fumar , Protetores Solares/uso terapêutico , Telangiectasia/etiologia
2.
PLoS One ; 8(2): e55116, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23390516

RESUMO

Tight junction (TJ) proteins are involved in a number of cellular functions, including paracellular barrier formation, cell polarization, differentiation, and proliferation. Altered expression of TJ proteins was reported in various epithelial tumors. Here, we used tissue samples of human cutaneous squamous cell carcinoma (SCC), its precursor tumors, as well as sun-exposed and non-sun-exposed skin as a model system to investigate TJ protein alteration at various stages of tumorigenesis. We identified that a broader localization of zonula occludens protein (ZO)-1 and claudin-4 (Cldn-4) as well as downregulation of Cldn-1 in deeper epidermal layers is a frequent event in all the tumor entities as well as in sun-exposed skin, suggesting that these changes result from chronic UV irradiation. In contrast, SCC could be distinguished from the precursor tumors and sun-exposed skin by a frequent complete loss of occludin (Ocln). To elucidate the impact of down-regulation of Ocln, we performed Ocln siRNA experiments in human keratinocytes and uncovered that Ocln downregulation results in decreased epithelial cell-cell adhesion and reduced susceptibility to apoptosis induction by UVB or TNF-related apoptosis-inducing ligand (TRAIL), cellular characteristics for tumorigenesis. Furthermore, an influence on epidermal differentiation was observed, while there was no change of E-cadherin and vimentin, markers for epithelial-mesenchymal transition. Ocln knock-down altered Ca(2+)-homeostasis which may contribute to alterations of cell-cell adhesion and differentiation. As downregulation of Ocln is also seen in SCC derived from other tissues, as well as in other carcinomas, we suggest this as a common principle in tumor pathogenesis, which may be used as a target for therapeutic intervention.


Assuntos
Carcinoma de Células Escamosas/genética , Transformação Celular Neoplásica/efeitos da radiação , Transição Epitelial-Mesenquimal/efeitos da radiação , Regulação Neoplásica da Expressão Gênica/efeitos da radiação , Queratinócitos/efeitos da radiação , Ocludina/genética , Neoplasias Cutâneas/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Cálcio/metabolismo , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Adesão Celular/efeitos da radiação , Diferenciação Celular/efeitos da radiação , Transformação Celular Neoplásica/metabolismo , Transformação Celular Neoplásica/patologia , Claudinas/genética , Claudinas/metabolismo , Feminino , Homeostase/efeitos da radiação , Humanos , Queratinócitos/citologia , Queratinócitos/metabolismo , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Ocludina/antagonistas & inibidores , Ocludina/metabolismo , RNA Interferente Pequeno/genética , Transdução de Sinais/efeitos da radiação , Neoplasias Cutâneas/metabolismo , Neoplasias Cutâneas/patologia , Junções Íntimas/metabolismo , Junções Íntimas/patologia , Junções Íntimas/efeitos da radiação , Adulto Jovem , Proteína da Zônula de Oclusão-1/genética , Proteína da Zônula de Oclusão-1/metabolismo
4.
J Invest Dermatol ; 128(4): 906-16, 2008 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-17914452

RESUMO

Tight Junction (TJ) proteins have been shown to exert a barrier function within the skin. Here, we study the fate of TJ proteins during the challenge of the skin by bacterial colonization and infection. We investigated the influence of various exfoliative toxin-negative Staphylococcus strains on TJ, adherens junction (AJ), desmosomal proteins, and actin in a human keratinocyte infection culture and in a porcine skin infection model. We found that the pathogen Staphylococcus aureus downregulates TJ and subsequently AJ and desmosomal proteins, including atypical protein kinase C, an essential player in TJ formation, at the cell-cell borders of keratinocytes in a time and concentration dependent manner. Little changes in protein and RNA levels were seen, indicating redistribution of proteins. In cultured keratinocytes, a reduction of transepithelial resistance was observed. Staphylococcus epidermidis shows only minor effects. All strains induced enhanced expression of occludin and ZO-1 at the beginning of colonization/infection. Thus, we demonstrate that TJ are likely to be involved in skin infection of exfoliative toxin-negative S. aureus. As we did not find a change in actin, and as changes of TJ preceded alterations of AJs and desmosomes, we suggest that S. aureus targets TJ.


Assuntos
Epiderme/microbiologia , Proteínas de Membrana/metabolismo , Infecções Estafilocócicas/metabolismo , Staphylococcus aureus , Staphylococcus epidermidis , Junções Íntimas/microbiologia , Actinas/metabolismo , Junções Aderentes/metabolismo , Animais , Desmossomos/metabolismo , Modelos Animais de Doenças , Epiderme/metabolismo , Humanos , Proteínas de Membrana/análise , Ocludina , Fosfoproteínas/metabolismo , Infecções Estafilocócicas/microbiologia , Junções Íntimas/química , Junções Íntimas/metabolismo , Proteína da Zônula de Oclusão-1
5.
J Invest Dermatol ; 127(10): 2453-62, 2007 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-17495958

RESUMO

Cutaneous wound healing is a well-coordinated process that includes inflammation, proliferation, and differentiation. Activator protein 1 (AP-1) subunits have been implicated in the regulation of genes important for these processes and have been shown to be involved in wound healing. However, investigation of human healing and non-healing wounds in vivo and ex vivo, and the comparative analysis of several members of the Jun and Fos families are still missing. Here, we show that normal human epidermal wound healing is biphasic. In the first phase all AP-1 subunits investigated, that is c-Jun, Jun B, Jun D, c-Fos, and Fos B are absent from the nuclei at the wound margins/leading edges. This downregulation coincides with that of the gap junction protein connexin 43. Later on, c-Jun, Jun B, Jun D, and c-Fos reappear in the nuclei of the leading edges in a time-dependent manner. In non-healing wounds, a more intensive staining of keratinocytes at the wound margins is often observed. Our findings suggest that coordinated down- and upregulation of the various AP-1 subunits in the course of epidermal wound healing is important for its undisturbed progress, putatively by influencing inflammation and cell-cell communication.


Assuntos
Epiderme/metabolismo , Fator de Transcrição AP-1/metabolismo , Cicatrização/fisiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Diferenciação Celular/fisiologia , Proliferação de Células , Conexina 43/metabolismo , Regulação para Baixo/fisiologia , Epiderme/patologia , Feminino , Regulação da Expressão Gênica/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas Proto-Oncogênicas c-fos/metabolismo , Proteínas Proto-Oncogênicas c-jun/metabolismo , Regulação para Cima/fisiologia
6.
Endocr Rev ; 27(6): 677-706, 2006 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-16877675

RESUMO

For many decades, androgens have dominated endocrine research in hair growth control. Androgen metabolism and the androgen receptor currently are the key targets for systemic, pharmacological hair growth control in clinical medicine. However, it has long been known that estrogens also profoundly alter hair follicle growth and cycling by binding to locally expressed high-affinity estrogen receptors (ERs). Besides altering the transcription of genes with estrogen-responsive elements, 17beta-estradiol (E2) also modifies androgen metabolism within distinct subunits of the pilosebaceous unit (i.e., hair follicle and sebaceous gland). The latter displays prominent aromatase activity, the key enzyme for androgen conversion to E2, and is both an estrogen source and target. Here, we chart the recent renaissance of estrogen research in hair research; explain why the hair follicle offers an ideal, clinically relevant test system for studying the role of sex steroids, their receptors, and interactions in neuroectodermal-mesodermal interaction systems in general; and illustrate how it can be exploited to identify novel functions and signaling cross talks of ER-mediated signaling. Emphasizing the long-underestimated complexity and species-, gender-, and site-dependence of E2-induced biological effects on the hair follicle, we explore targets for pharmacological intervention in clinically relevant hair cycle manipulation, ranging from androgenetic alopecia and hirsutism via telogen effluvium to chemotherapy-induced alopecia. While defining major open questions, unsolved clinical challenges, and particularly promising research avenues in this area, we argue that the time has come to pay estrogen-mediated signaling the full attention it deserves in future endocrinological therapy of common hair growth disorders.


Assuntos
Estrogênios/fisiologia , Folículo Piloso/fisiologia , Transdução de Sinais/fisiologia , Animais , Folículo Piloso/citologia , Folículo Piloso/crescimento & desenvolvimento , Humanos
7.
J Investig Dermatol Symp Proc ; 10(3): 243-6, 2005 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-16382674

RESUMO

In this study, it was investigated how estrogens (17-beta-estradiol, E2) affect the estrogen receptor (ER) expression and gene regulation of male versus female human scalp hair follicles in vitro. Anagen VI follicles from frontotemporal scalp skin were microdissected and organ-cultured for up to 9 d in the presence of E2 (1-100 nm). Immunohistochemistry was performed for ERbeta-expression, known to be predominant in human scalp hair follicles, and for TGF-beta2-expression (as negative key hair growth modulator), and E2-responsive genes in organ-cultured human scalp hair follicles (48 h, 10 nM) were explored by cDNA microarray, using a commercial skin focus chip (Memorec, Cologne, Germany). The distribution pattern of ERbeta and TGF-beta2-immunoreactivity differed between male and female hair follicles after 48 h culture. Of 1300 genes tested, several genes were regulated sex-dependent differently. The study reveals substantial sex-dependent differences in the response of frontotemporal human scalp hair follicles to E2. Recognition and systematic dissection of the E2-dependent gene regulation will be crucial for the development of more effective, gender-tailored management strategies for female versus male pattern balding.


Assuntos
Estradiol/metabolismo , Receptor beta de Estrogênio/metabolismo , Folículo Piloso/metabolismo , Couro Cabeludo/metabolismo , Alopecia/metabolismo , Alopecia/terapia , Estrogênios/metabolismo , Feminino , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Humanos , Imuno-Histoquímica , Técnicas In Vitro , Masculino , Análise de Sequência com Séries de Oligonucleotídeos , Caracteres Sexuais , Fator de Crescimento Transformador beta/metabolismo
8.
Endocrinology ; 146(3): 1214-25, 2005 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-15591132

RESUMO

Although 17beta-estradiol (E2) is recognized as a potent hair growth modulator, our knowledge of estrogen function, signaling, and target genes in hair biology is still very limited. Between the two recognized estrogen receptors (ERs), ER alpha and ER beta, only ER alpha had been detected in murine skin. Here we show that ER alpha, ER beta, and ER beta ins are all expressed throughout the murine hair cycle, both at the protein and RNA level, but show distinct expression patterns. We confirm that topical E2 arrests murine pelage hair follicles in telogen and demonstrate that E2 is a potent inducer of premature catagen development. The ER antagonist ICI 182.780 does not induce anagen prematurely but accelerates anagen development and wave spreading in female mice. ER beta knockout mice display accelerated catagen development along with an increase in the number of apoptotic hair follicle keratinocytes. This suggests that, contrary to previous concepts, ER beta does indeed play a significant role in murine hair growth control: whereas the catagen-promoting properties of E2 are mediated via ER alpha, ER beta mainly may function as a silencer of ER alpha action in hair biology. These findings illustrate the complexity of hair growth modulation by estrogens and suggest that one key to more effective hair growth manipulation with ER ligands lies in the use of selective ER alpha or -beta antagonists/agonists. Our study also underscores that the hair cycling response to estrogens offers an ideal model for studying the controls and dynamics of wave propagation in biological systems.


Assuntos
Estradiol/análogos & derivados , Receptor alfa de Estrogênio/metabolismo , Receptor beta de Estrogênio/metabolismo , Estrogênios/metabolismo , Cabelo/metabolismo , Animais , Apoptose , Estradiol/metabolismo , Estradiol/farmacologia , Receptor beta de Estrogênio/genética , Feminino , Fulvestranto , Cabelo/fisiologia , Imuno-Histoquímica , Ligantes , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Modelos Anatômicos , Fenótipo , RNA/metabolismo , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Pele/metabolismo , Fatores de Tempo
9.
Regul Pept ; 124(1-3): 19-25, 2005 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-15544837

RESUMO

INTRODUCTION: Recent studies have shown that neurotrophins (NTs) are involved in inflammatory processes. Elevated plasma levels of NTs were found allergic diseases with the highest levels in allergic asthma. However, the exact cellular sources involved in the regulation and release of neurotrophins in allergic inflammation are still not well defined. OBJECTIVE: The aim of this study was to assess whether monocytes of allergic and non-allergic subjects produce, store and release the neurotrophins NGF, BDNF and NT-3. METHODS: Monocytes of allergic and non-allergic donors were purified by immunomagnetic selection. APAAP-staining for the presence of NTs and their receptors was performed. RT-PCR and Western blot evaluated the production and storage of NTs. Monocytes were incubated and supernatants were collected for measurement of neurotrophic factors after stimulation with lipopolysaccharide (LPS) as inflammatory stimulus. The neurotrophin content in lysates and cell culture supernatants was determined by ELISA. RESULTS: Human monocytes express the neurotrophins NGF, BDNF and NT-3 but also their specific receptors TrkA, TrkB and TrkC. RT-PCR amplification of isolated mRNA demonstrated expression of the examined neurotrophins. Proteins were detectable by Western blot. NTs were found in the monocyte lysates and supernatants at different levels in allergic and non-allergic donors. Cell stimulation with LPS leads to release of NGF and NT3. CONCLUSIONS: Monocytes, produce, store and release NGF, BDNF and NT-3. They are a possible source of elevated neurotrophin levels found in allergy and asthma.


Assuntos
Asma/metabolismo , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Monócitos/metabolismo , Fator de Crescimento Neural/metabolismo , Neurotrofina 3/metabolismo , Adolescente , Adulto , Asma/genética , Asma/imunologia , Asma/patologia , Western Blotting , Fator Neurotrófico Derivado do Encéfalo/biossíntese , Fator Neurotrófico Derivado do Encéfalo/genética , Células Cultivadas , Meios de Cultura , Eletroforese em Gel de Poliacrilamida , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Monócitos/imunologia , Fator de Crescimento Neural/biossíntese , Fator de Crescimento Neural/genética , Neurotrofina 3/biossíntese , Neurotrofina 3/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptores Proteína Tirosina Quinases/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa
11.
J Invest Dermatol ; 122(1): 7-13, 2004 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-14962083

RESUMO

Estrogen receptor ligands are important modulators of skin physiology and are involved in the control of normal hair follicle cycling. Here, we have studied the effects of topically applied 17-beta-estradiol on pathologic hair follicle cycling as seen during chemotherapy-induced alopecia, one of the major unresolved problems of clinical oncology. For this study we employed a well-established murine model that mimics chemotherapy-induced alopecia in humans. For precisely quantifying the area of hair loss and hair regrowth in this model in vivo, we developed a simple planimetric assay (dotmatrix planimetry). We show that topical 17-beta-estradiol significantly alters the cycling response of murine follicles to cyclophosphamide, whereas the estrogen antagonist ICI 182.780 exerted no such effects. Initially, topical 17-beta-estradiol enhanced chemotherapy-induced alopecia significantly by forcing the follicles into the dystrophic catagen response pathway to hair follicle damage, whereas follicles treated by ICI 182.780 or vehicle shifted into the dystrophic anagen response pathway. Consequently, the regrowth of normally pigmented hair shafts after chemotherapy-induced alopecia was significantly accelerated in the 17-beta-estradiol treated group. Our data encourage one to explore topical estrogens as a potential stimulant for hair re-growth after chemotherapy-induced alopecia.


Assuntos
Alopecia/tratamento farmacológico , Estradiol/análogos & derivados , Estradiol/farmacologia , Cabelo/efeitos dos fármacos , Cabelo/crescimento & desenvolvimento , Administração Tópica , Alopecia/induzido quimicamente , Animais , Antineoplásicos Alquilantes , Ciclofosfamida , Antagonistas de Estrogênios/farmacologia , Feminino , Fulvestranto , Cabelo/patologia , Camundongos , Camundongos Endogâmicos C57BL
12.
Am J Pathol ; 162(5): 1611-21, 2003 May.
Artigo em Inglês | MEDLINE | ID: mdl-12707045

RESUMO

Here, we provide the first study of prolactin (PRL) and prolactin receptor (PRLR) expression during the nonseasonal murine hair cycle, which is, in contrast to sheep, comparable with the human scalp and report that both PRL and PRLR are stringently restricted to the hair follicle epithelium and are strongly hair cycle-dependent. In addition we show that PRL exerts functional effects on anagen hair follicles in murine skin organ culture by down-regulation of proliferation in follicular keratinocytes. In telogen follicles, PRL-like immunoreactivity was detected in outer root sheath (ORS) keratinocytes. During early anagen (III to IV), the developing inner root sheath (IRS) and the surrounding ORS were positive for PRL. In later anagen stages, PRL could be detected in the proximal IRS and the inner layer of the ORS. The regressing (catagen) follicle showed a strong expression of PRL in the proximal ORS. In early anagen, PRLR immunoreactivity occurred in the distal part of the ORS around the developing IRS, and subsequently to a restricted area of the more distal ORS during later anagen stages and during early catagen. The dermal papilla (DP) stayed negative for both PRL and PRLR throughout the cycle. Telogen follicles showed only a very weak PRLR staining of ORS keratinocytes. The long-form PRLR transcript was shown by real-time polymerase chain reaction to be transiently down-regulated during early anagen, whereas PRL transcripts were up-regulated during mid anagen. Addition of PRL (400 ng/ml) to anagen hair follicles in murine skin organ culture for 72 hours induced premature catagen development in vitro along with a decline in the number of proliferating hair bulb keratinocytes. These data support the intriguing concept that PRL is generated locally in the hair follicle epithelium and acts directly in an autocrine or paracrine manner to modulate the hair cycle.


Assuntos
Ciclo Celular/fisiologia , Folículo Piloso/fisiologia , Cabelo/crescimento & desenvolvimento , Prolactina/genética , Receptores da Prolactina/genética , Animais , Sequência de Bases , Primers do DNA , Células Epiteliais/citologia , Células Epiteliais/fisiologia , Feminino , Regulação da Expressão Gênica , Cabelo/citologia , Folículo Piloso/citologia , Humanos , Queratinócitos/citologia , Queratinócitos/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , Modelos Animais , Lactogênio Placentário/genética , Reação em Cadeia da Polimerase , Pele/citologia , Fenômenos Fisiológicos da Pele
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