RESUMO
El carcinoma cutáneo de células escamosas (CCE) es el segundo cáncer de piel ms común en humanos, el cual puede llegar a ser invasivo y mostrar un curso agresivo. El CCE inicia en las células escamosas de la capa epidérmica. Así mismo, la epidermis se compone de tejido queratinizado que se regenera continuamente a partir de células basales y reemplaza a las células muertas. Estudios sobre el proceso de diferenciación celular, muestran que los microRNAs (miRNAs) están involucrados en el proceso de formación de la piel, y se ha reportado que alteraciones en la transcripción, procesamiento y expresión de los miRNAs afecta a la señalización celular, esencial en la proliferación, invasión, apoptosis y diferenciación células malignas. Los miRNAs son una familia de reguladores epigenéticos de pequeñas moléculas endógenas no codificantes de RNAs de aproximadamente 25 nucleótidos de longitud, y están involucrados en la patogénesis de cáncer en humanos como reguladores de factores de crecimiento transformantes y metástasis. Se hizo una revisión sistemática usando las principales bases de datos bibliográficas (PubMed/MEDLINE, Science) y revistas públicas en internet. Los criterios de inclusión y exclusión fueron predefinidos (carcinoma cutáneo, miRNAs, biogénesis) y también un conjunto de variables para analizar las características de los artículos seleccionados (expresión y el papel de los miRNAs en el CCE, que no han sido bien estudiadas).
The cutaneous squamous cell carcinoma (cSCC) is the second most common skin cancer in humans, which can become invasive and show an aggressive course. CSCC starts in the epidermal layer of squamous cells. Also, the epidermis is composed of keratinized tissue that continuously regenerate from basal cells and replace the dead cells. Studies about cell differentiation process, shows that microRNAs (miRNAs) are involved in the process of skin formation, and has been reported that alterations intranscription, processing and expression of miRNAs, affect the function of the cell signaling, essential the proliferation, invasion, apoptosis and differentiation of malignant cells. MiRNAs are an epigenetic regulators family of small noncoding endogenous molecules of RNAs, about 25 nucleotides in length, and are involved in the pathogenesis of human cancer in the regulation of transformant growth factors and metastasis. We performed a systematic review using major electronic bibliographic databases (PubMed/MEDLINE, Sciencie) and public journals on the internet. Inclusion and exclusion criteria were pre-defined (cutaneous carcinoma, miRNAs, and biogenesis) and also a set of variables to analyze the characteristics of the selected reports (the expression and role of miRNAs in the cSCC, what has not been well studied).
Assuntos
Humanos , Carcinoma de Células Escamosas/genética , MicroRNAs/genética , Neoplasias Cutâneas/genética , MicroRNAs/metabolismoRESUMO
In subacute cutaneous lupus eryhematosus (SCLE) the cutaneous antigens constitute the main source of Ro and La autoantigens. The aim of this investigation was to demonstrate if UV light increases the availability of Ro autoantigen in the skin, also the blocking effect of Ac-DEVD-CMK a caspase inhibitor was assessed. For this purpose newborn Balb/c mice were UVB irradiated (5-30 mJ/cm(2)) equivalent to a moderate to severe sunburn. Animals were injected with monoclonal anti-Ro antibodies from SCLE patients. Apoptosis was also induced by anti-Fas antibody injection. Skin samples were examined by direct immunofluoresence, by TUNEL, and the expression of caspase 3 by RT-PCR. Major findings of present studies were: 1. UVB irradiation and anti-Fas induced apoptosis of keratinocytes. 2. Apoptosis redistribute the Ro antigen on cell surface and is better triggered by Ro antibody. 3. The caspase 3 inhibitor Ac-DEVD-CMK decreases the availability of Ro autoantigen in epidermis and prevents deposition of anti-Ro. In conclusion, the caspase pathway would be blocked to avoid anti-Ro deposition along skin; this finding would be a prospect in the treatment of SCLE patients.
Assuntos
Apoptose , Autoanticorpos/administração & dosagem , Lúpus Eritematoso Cutâneo/metabolismo , Lúpus Eritematoso Cutâneo/patologia , Transtornos de Fotossensibilidade/etiologia , Ribonucleoproteínas/metabolismo , Raios Ultravioleta , Clorometilcetonas de Aminoácidos/farmacologia , Animais , Apoptose/fisiologia , Relação Dose-Resposta à Radiação , Lúpus Eritematoso Cutâneo/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Ribonucleoproteínas/imunologia , Pele/efeitos dos fármacos , Pele/imunologiaRESUMO
Fas ligand (L) is a membrane protein from the tumor necrosis factor (TNF) family. It induces apoptosis upon contact with its Fas/CD95/APO1 receptor. Trimerization of FasL on the surface of effector cells is essential in the binding of the Fas trimer of the target cells. The receptor then recruits an adaptor and caspase-like proteins which lead apoptosis. This paper reports on the fate of FasL in HEp-2 cells committed to apoptosis by induction with campthotecin. Our main results demonstrated that in non-apoptotic cells, FasL aggregates in the cytoplasm forming trimers of 120 kDa. Apoptosis increases the trimeric FasL species, but also induces its dissociation into monomers of 35 kDa. In conclusion, camptothecin appears to perturb the Fas and FasL segregation in the cytoplasm by promoting the transit of FasL to the cell surface, thus fostering a process of autocrine or paracrine apoptosis. FasL is trimerized prior to Fas/FasL complex formation, and after apoptosis, FasL undergoes an intense turnover.
Assuntos
Apoptose/efeitos dos fármacos , Camptotecina/farmacologia , Proteína Ligante Fas/química , Proteína Ligante Fas/metabolismo , Clorometilcetonas de Aminoácidos/farmacologia , Caspase 3/genética , Linhagem Celular Tumoral , Fragmentação do DNA/efeitos dos fármacos , Desoxirribonucleases/genética , Proteína Ligante Fas/genética , Humanos , Marcação In Situ das Extremidades Cortadas , Proteínas de Ligação a Poli-ADP-Ribose , Estrutura Quaternária de Proteína , Transporte Proteico/efeitos dos fármacos , Frações Subcelulares/efeitos dos fármacos , Transcrição Gênica/efeitos dos fármacos , Receptor fas/genéticaRESUMO
OBJECTIVE: Present study addresses the issue whether cellular antigens recognised by antinuclear autoantibodies are driven by apoptosis. MATERIALS AND METHODS: HEp-2 cells were committed to apoptosis by camptothecin; DNA fragmentation and FasL and Bax expression monitored apoptosis. Autoantigens were probed by indirect immunofluorescence and Western blot with autoantibodies or monoclonals against: DNA, Ro60, La, U1-RNP, CENP-B, DNA Topoisomerase I, Jo-1 and NuMA. A comparison of antinuclear antibody reactivity between living and apoptotic cells was performed by ELISA. RESULTS: Apoptotic changes such as chromatin fragmentation, blebs and apoptotic bodies were induced with 20 mM camptothecin. Autoantigens were better detected in apoptotic cells. U1-RNP, Jo1, DNA-Topoisomerase I, CENP-B and NuMA exhibited fragmentation and redistribution as a consequence of apoptosis; in contrast, Ro60 and La ribonucleoproteins did not show proteolysis. Additionally the ELISA titers of antinuclear antibodies were higher in apoptotic cells than in normal cells. CONCLUSION: Apoptosis induces molecular changes in different autoantigens, this modification increases the antigen-driven response of autoantibodies such as anti-RNP, anti-DNA Topoisomerase I, anti-CENP-B and anti-Jo1. Apoptotic changes would contribute to break down the tolerance in autoimmune connective tissue disease.
Assuntos
Anticorpos Antinucleares/imunologia , Apoptose/imunologia , Autoantígenos/imunologia , Proteínas Proto-Oncogênicas c-bcl-2 , Apoptose/efeitos dos fármacos , Autoantígenos/metabolismo , Western Blotting , Camptotecina/farmacologia , Linhagem Celular , Fragmentação do DNA , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/imunologia , Células Epiteliais/patologia , Proteína Ligante Fas , Técnica Indireta de Fluorescência para Anticorpo , Humanos , Glicoproteínas de Membrana/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Ribonucleoproteína Nuclear Pequena U1/imunologia , Proteína X Associada a bcl-2RESUMO
OBJECTIVE: The goals of the current work are: 1) to examine the epidermal deposition of anti-RNP IgG human autoantibodies in neonatal BALB/c mice; 2) to look for immunoregulatory effects of anti-idiotypes allowing one to inhibit the epidermal deposition of anti-RNP antibodies; and 3) to elicit antinuclear antibodies in adult BALB/c mice by internal images of anti-idiotypes. MATERIALS AND METHODS: Anti-idiotype antibodies were produced with human anti-RNP IgG obtained by ion exchange chromatography; F(ab')2 fragments were recovered from pepsin digestion and were purified using Sephacryl S-300. F(ab')2 fragments were then used to immunize New Zealand rabbits. RESULTS: The anti-RNP IgG recognized the 70 kDa protein and the A (31 kDa) and C (19 kDa) proteins, while the anti-idiotype antibody specifically recognized the light or heavy chain of the anti-RNP (Fab')2 fragments. Additionally, anti-idiotypes recognized the anti-RNP IgG from some sera, but not the IgG from other specificities or from normal IgG. When anti-RNP IgG was injected intraperitoneally into BALB/c mice it induced immune complex deposition in the epidermis and at the dermal-epidermal junction. Previous injection of anti-idiotype antibodies abrogated the anti-RNP IgG deposits. Vaccination with anti-idiotypes elicit antinuclear antibodies in adult BALB/c mice. CONCLUSIONS: Anti-idiotype antibodies abrogate in vitro the antinuclear antibody deposition in neonatal BALB/c mice. Anti-idiotype antibodies elicit antinuclear antibodies in adult BALB/c mice.
Assuntos
Anticorpos Antinucleares/imunologia , Autoantígenos/imunologia , Dermatite/imunologia , Doenças do Complexo Imune/imunologia , Imunoglobulina G/imunologia , Animais , Animais Recém-Nascidos , Anticorpos Antinucleares/administração & dosagem , Autoantígenos/administração & dosagem , Dermatite/prevenção & controle , Humanos , Doenças do Complexo Imune/prevenção & controle , Imunização Passiva , Imunoglobulina G/administração & dosagem , Idiótipos de Imunoglobulinas , Camundongos , Camundongos Endogâmicos BALB C , Coelhos , Pele/imunologia , Pele/patologia , Proteínas Centrais de snRNPRESUMO
La yucuyahui (zoapatle-Montanoa tomentosa) es una planta silvestre con propiedades oxitócicas. Tomaron infusiones de esta planta durante el trabajo de parto ocho embarazadas y sus recién nacidos evolucionaron con signos de depresión cardio-respiratoria que requirió de apoyo vital básico o avanzado para su recuperación. La efectividad de estas maniobras se midió de acuerdo al puntaje de Apgar que promediado para el primer minuto fue de 4.5 y se incrementó a los 10 minutos por efecto de las maniobras citadas, a 7.4 (p< 0.05). El tiempo para la recuperación total de los neonatos fue de 11.9 horas (10 minutos - 36 horas). Se encontró una correlación negativa entre el número de infusiones administradas a las madres y la calificación de Apgar al minuto (r=- 0.65), sugiriendo que a mayor número de infusiones menor puntaje y por tanto mayor depresión. La administración simultánea de bebidas alcohólicas a tres de las embarazadas pareció no influir en la gravedad de la depresión; la recuperación de los neonatos expuestos al etanol fue más rápida que en aquellos no expuestos: 2.4 vs. 9.7 horas, p< 0.05. Se desconoce cuál es el mecanismo íntimo de acción de Montanoa tomentosa, se especula que pudiera ser similar al de otros oxitócicos como la oxitocina y los alcaloides del cornezuelo de centeno, con los que guarda semejanzas en sus efectos uterotónicos y sistémicos