Transforming growth factor beta 1 (TGF-beta 1) is a potent autocrine growth inhibitor of lymphocytes. In this study, the expression of TGF-beta 1 binding proteins was characterized on murine splenic T cells. With an affinity cross-linking method and by neutralizing antibodies to TGF-beta 1, [125I] TGF-beta 1 was found to bind to three cell surface-binding proteins (280-200 kD, 95-85 kD, 65 kD) that were differentially expressed on resting and mitogen-stimulated T cells. Freshly prepared (resting) T cells were found to constitutively express the 95-85-kD form of these binding proteins, whereas mitogenic stimulation by either concanavalin-A (Con-A), interleukin-1 (IL-1), interleukin-2 (IL-2), or 12-tetradecanoyl-phorbol-13-acetate (TPA) for 12-72 h induced the appearance of all forms of the TGF-beta 1 binding proteins (280-200 kD, 95-85 kD, and 65 kD). Furthermore, antibodies that neutralized the biologic action of TGF-beta 1 also blocked the binding of [125I] TGF-beta 1 to all three binding proteins, suggesting that these binding proteins are involved with signal transduction. These results suggest that the expression of the TGF-beta 1 receptor on T cells is regulated by T cell mitogenic signals and that a regulatory relationship may exist between T cell growth-promoting cytokines (IL-1 and IL-2) and the T cell growth inhibitor, TGF-beta 1.
The growth inhibitory activity in conditioned medium of African green monkey kidney epithelial (BSC-1) cells that has been shown to arise, at least in part, from transforming growth factor beta 2 (TGF-beta 2) [Hanks, S. K., Armour, R., Baldwin, J. H., Maldonado, F., Spiess, J., & Holley, R. W. (1988) Proc. Natl. Acad. Sci. U.S.A. 85, 79-82] was tested for growth inhibitory activity prior to and following acidification. Similar to TGF-beta 1 from human platelets, the inhibitory activity from BSC-1 cells demonstrated an 8-10-fold stimulation following acidification, showing that the activity was secreted from the cells in latent form. Conditioned medium from BSC-1 cells was collected, acidified, and fractionated by procedures that separate TGF-beta 1 and -2. Biological activity was assayed by using the BSC-1 cell proliferation assay. Two active proteins with properties similar to known TGF-beta 1 and TGF-beta 2 were identified. Identity was confirmed by using immunological and amino acid sequencing techniques. These results were consistent with Northern blot analysis of total BSC-1 RNA, using cDNA probes for TGF-beta 1 and TGF-beta 2, which demonstrated strong signals for both mRNAs. Metabolic labeling in conjunction with two-dimensional gel electrophoresis revealed that the cells secrete approximately 10% TGF-beta 1 and 90% TGF-beta 2.
Introducción: actualmente existe un importante descenso de los niveles de adherencia a la dieta mediterránea y actividad física en personas jóvenes, lo cual influye en el estado de salud. Una preocupación que se puede constatar en los análisis que se realizan en diversos estudios así como en programas de intervención implementados desde las instituciones. El objetivo fue determinar la relación existente entre el nivel de actividad física y la calidad de la dieta mediterránea en escolares de Educación Secundaria Obligatoria considerando el curso educativo y el sexo. Material y métodos: estudio descriptivo-transversal realizado con 194 escolares españoles de 12-16 años seleccionados mediante muestreo no probabilístico intencional procedentes de Murcia. Se valoró la calidad de la dieta mediterránea (CD) a través del cuestionario KIDMED y la actividad física (AF) a través del cuestionario InternationalPhysical Activity Questionnaire for Adolescents. El análisis estadístico fue llevado a cabo mediante las pruebas T Student, ANOVA y análisis de regresión lineal. Resultados: Los resultados de los análisis mostraron diferencias significativas en el nivel de AF según el tramo educativo en varones (p< 0,047) y considerando el total (p< 0,017). Respecto a las diferencias en el nivel de AF en función de la CD, se encontraron diferenciassignificativas entre un nivel alto de CD y sus pares homólogos con un nivel bajo (p< 0,001). Por último, tras ajustar por sexo y edad, se encontró asociación entre la AF y la CD (p < 0,001) con un valor de R2 = 0,521. Conclusiones: una mayor actividad física se relaciona con una mayor calidad de la dieta en escolares de Educación Secundaria Obligatoria. Existe la necesidad de diseñar desde la institución educativa y sanitaria programas formativos, tanto para docentes como discentes, que permitan el desarrollo de conductas dirigidas hacia una perspectiva saludable que perdure hasta la adultez.
In myeloproliferative neoplasms (MPN), both malignant and non-malignant clones contribute to inflammatory cytokine production mediated by JAK/STAT activation. Available JAK signaling-only inhibitors, however, do not reverse medullary fibrosis. As the NF-κ B pathway also plays a critical role, we previously demonstrated the importance, in MPN, of miR-146a, a negative regulator of the NF-kB pathway by inhibiting IRAK1/TRAF6 (Leukemia 2020). Indeed, miR-146a -/-(KO) mice develop a myelofibrosis (MF)-like phenotype and show an increase in p-STAT3 with aging.
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