Phorbol esters and CAMP differentially regulate the expression of CD4 and CD8 in human thymocytes

BACKGROUND: Intrathymic development and selection of the T lymphocyte repertoire is restricted by the interactions of the T cell antigen receptor and CD4 or CD8 co-receptors with self major histocompatibility complex molecules. Positive or negative selection depends on a tight regulatory control of CD4 and CD8 expression. Determining the intracellular signals that differentially regulate the expression of CD4 and CD8 is important to understand the mechanisms that are implicated in selection of single positive CD4(+)CD8(-) or CD4(-)CD8(+). RESULTS: The present study shows that stimulation of human thymocytes by phorbol esters or cAMP result in a differential regulation of CD4 and CD8 expression, both at the mRNA and cell surface glycoprotein level. CONCLUSIONS: The differential regulation of CD4 and CD8 gene expression suggests that the selective activation of protein kinase C (PKC) and cAMP-dependent protein kinases (PKA) may be required for the selection of single positive CD4(+)CD8(-) and CD4(-)CD8(+) cells during Intrathymic differentiatio

The SNP at −592 of human IL-10 gene is associated with serum IL-10 levels and increased risk for human papillomavirus cervical lesion development

BACKGROUND: Women with Human Papilloma Virus (HPV) persistence are characterized by high levels of IL-10 at cervix. We have determined whether polymorphisms of IL-10 gene promoter might be associated with increased risk of squamous intraepithelial cervical lesions (SICL) and whether exist significative differences of IL-10 mRNA expression at cervix and systemic and serum IL-10 protein between SICL cases and non-Cervical Lesions (NCL). METHODS: Peripheral blood samples from SICL (n = 204) and NCL (n = 166) were used to detect IL-10 promoter polymorphisms at loci -592A/C (rs1800872), -819C/T (rs1800871), -1082A/G (rs1800896), -1352A/G (rs1800893), by allelic discrimination and to evaluate serum IL-10 protein. Cervical epithelial scrapings from NCL and biopsies from SICLs were used for HPV-typing and to evaluate IL-10 mRNA expression level. The systemic and local IL-10 mRNA expression levels were measured by real time-PCR. Genotypic and allelic frequencies of the selected polymorphisms were analyzed by logistic regression, adjusting by age and HPV-genotype, to determine the association with SICL. RESULTS: No significant differences were found between genotype frequencies at loci −819, -1082, and −1352. Individuals carrying at least one copy of risk allele A of polymorphism −592 had a two-fold increased risk of developing SICL [adjusted odds ratio (OR), 2.02 (95% CI, 1.26-3.25), p = 0.003], compared to NCL. The IL-10 mRNA expression and serum IL-10 protein, were significantly higher in SICL cases (p < 0.01), being higher in patients carrying the risk allele A. CONCLUSIONS: The −592 polymorphism is associated with increased risk of SICL and can serve as a marker of genetic susceptibility to SICL among Mexican women. According to IL-10 levels found in SICL, IL-10 can be relevant factor for viral persistence and progression disease

High relative abundance of firmicutes and increased TNF-α levels correlate with obesity in children

Objective. To investigate the correlation among pro- or anti-inflammatory cytokines and the two main gut microbiota phyla in obese children. Materials and methods. Anthropometric data were obtained from 890 children under 14 years old to determine the degree of obesity. Serum cytokine concentration was measured by ELISA. Relative abundance of gut microbiota in feces was evaluated by quantitative RealTime PCR assays. Results. Anthropometric and biochemical parameters were statistically higher in overweigth/ obese children (OW/O) than in lean (NW), Increased TNF-α levels were found in obese children that also have a high relative abundance of Firmicutes. Conclusions. Obese children have a high relative abundance of Firmicutes that correlates with increased levels of TNF-α. This is the first study that shows a relation between Firmicute abundance and TNF-α serum concentration in obese children

Medicina genómica aplicada a la salud pública An overview in genomic medicine and public health

La genómica, visualizada como una disciplina científica encargada del mapeo, secuenciación y análisis de los genomas, ha facilitado la identificación y comprensión de las formas de organización y función de los genes de los organismos, lo cual ha generado un amplio conocimiento de la estructura y la función de los genomas. La influencia de la genómica en la medicina ha creado una nueva visión acerca de la forma de percibir los episodios patológicos y fisiológicos, tras conocer la influencia de las variaciones genéticas sobre la susceptibilidad a la enfermedad. En la salud pública, mediante la epidemiología genética, el conocimiento genético ha promovido acciones individuales y poblacionales para evaluar el efecto de la distribución de los determinantes genéticos y su interacción con factores ambientales en la etiología de las enfermedades humanas. De modo adicional, la medicina genómica propone nuevos sistemas de diagnóstico, relaciones genéticas y alteraciones alimenticias, respuesta específica a diversos medicamentos y diseño de nuevos fármacos para grupos susceptibles. Sin embargo, los grandes avances de la medicina genómica en el campo de la salud aún son sólo promisorios.<br>Genomics, as a scientific discipline responsible for genome maps, sequencing and functional analysis of genomes, allows for continually expanding knowledge of the structure and function of genomes. The influence of genomics on medicine generates a new perspective for how we perceive health and disease, knowing the influence of genetic variations on susceptibility to disease. In the area of public health, genetic epidemiology translates genetic knowledge into individual and public actions, evaluating the effect of the distribution of genetic determinants and their interaction with environmental factors involved in the etiology of human diseases. In addition, genomic medicine suggests new diagnostic systems, genetic associations and nutritional disorders, specific responses to diverse drugs, and the design of new drugs for susceptible groups. And yet, the greatest advances in genomic medicine in the field of health are forthcoming

Factor de crecimiento transformante beta-1: estructura, función y mecanismos de regulación en cáncer

El factor de crecimiento transformante beta-1 (TGF-beta1) es sintetizado por muchas estirpes celulares como linfocitos, macrófagos y células dendríticas, y su expresión regula de manera autócrina o parácrina la diferenciación, proliferación y el estado de activación de éstas y muchas otras células. En general, el TGF-beta1 tiene propiedades pleiotrópicas en el contexto de la respuesta inmune durante el desarrollo de infecciones y procesos neoplásicos; sin embargo, los mecanismos de acción y regulación de la expresión de esta citocina aún no se comprenden del todo. En la presente revisión se describen las propiedades biológicas y los procesos moleculares que regulan la expresión del TGF-beta1, para entender los efectos de esta citocina durante la proliferación y la diferenciación celular. El conocimiento de los mecanismos moleculares de la regulación del TGF-beta1 puede representar una importante estrategia de tratamiento del cáncer. El texto completo en inglés de este artículo está disponible en: http://www.insp.mx/salud/index.html</A