Examinando por Autor "Morales, J."
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Ítem Interleukin-4 Selectively Inhibits Interleukin-2 Secretion by Lipopolysaccharide-Activated Dendritic Cells(Wiley, 2004-02) Sauma, D.; Michea, P.; Lennon-Dumenil, A.; Fierro, A.; Morales, J.; Rosemblatt, M.; Bono, M.Dendritic cells (DCs) generated in vitro from bone marrow precursors using granulocyte-macrophage colony-stimulating factor (GM-CSF) secrete interleukin-2 (IL-2) upon activation, an event probably associated to the initiation of adaptive immune responses. Additionally, they produce IL-12, a cytokine related to T-cell polarization. To analyse the effect of IL-4 on DC differentiation and function, we assessed the capacity of murine bone marrow dendritic cells (BMDCs) differentiated with GM-CSF in the presence or absence of IL-4 to produce IL-2 and IL-12 upon lipopolysaccharide (LPS) activation. We found that although IL-4 enhanced DC IL-12p70 production, it strongly impaired IL-2 secretion by BMDCs. This inhibition, which depends on the presence of IL-4 during LPS activation, is DC specific, as IL-4 did not affect IL-2 secretion by T cells. Interestingly, inhibition of DC IL-2 production did not prevent DC priming of T lymphocytes. These results illustrate a new putative role for IL-4 on the regulation of the immune response and should help clarify the controversial reports on the effect of IL-4 on DCs.Ítem Photodegradation of nimodipine and felodipine in microheterogeneous systems(Sociedad Chilena de Química, 2012) Brito, J.; Pozo, A.; García, C.; Núñez-Vergara, L.; Morales, J.; Günther, G.; Pizarro, N.The photochemical behavior of nimodipine (NIMO) and felodipine (FELO), photolabile drugs widely used as antihypertensive calcium channel blockers, is studied in constrained media. Specifically, we are interested in the kinetic analysis of 4-aryl-1,4-dihydropyridine photodegradation processes when they are incorporated in biological-mimicking systems like micelles or liposomes. In order to establish if the nature of the head of surfactant (ionic or nonionic) could be important modulating the photo-reactivity of these drugs, we studied the photodegradation of NIMO and FELO incorporated in micelles formed with sodium dodecyl sulfate (SDS, anionic), dodecyl-pyridinium chloride (DPC, cationic) and mono lauryl sucrose ester (MLS, nonionic) as surfactants. Additionally, the results of the photodegradation of these compounds in liposomes were also included. The results clearly indicate that both dihydropyridines studied, NIMO and FELO, are located near to the interface, but the surface charge of micelles does not affect neither, the photodegradation rate constant nor the photodegradation products profile. The absence of singlet oxygen generation in micellar media is consistent with the proposition of these 4-aryl-1,4-dihidropyridines located near to the interface of the micelle, where a polar environment is sensed. In addition, the ethanol preferential location on membranes and dihydropyridine enhanced photodegradation by alcohol presence are interesting results to consider in future research.Ítem Single and combined effect of retinoic acid and rapamycin modulate the generation, activity and homing potential of induced human regulatory T cells(Public Library of Science, 2017-07) Candia, E.; Reyes, P.; Covian, C.; Rodriguez, F.; Wainstein, N.; Morales, J.; Mosso, C.; Rosemblatt, M.; Fierro, J.A.Adoptive transfer of CD4+CD25+FOXP3+ regulatory T cells (Treg cells) has been successfully utilized to treat graft versus host disease and represents a promising strategy for the treatment of autoimmune diseases and transplant rejection. The aim of this study was to evaluate the effects of all-trans retinoic acid (atRA) and rapamycin (RAPA) on the number, phenotype, homing markers expression, DNA methylation, and function of induced human Treg cells in short-term cultures. Naive T cells were polyclonally stimulated and cultured for five days in the presence of different combinations of IL-2, TGF-β1, atRA and RAPA. The resulting cells were characterized by the expression of FOXP3, activation, surface and homing markers. Methylation of the Conserved Non-coding Sequence 2 was also evaluated. Functional comparison of the different culture conditions was performed by suppression assays in vitro. Culturing naive human T cells with IL-2/TGFβ1 resulted in the generation of 54.2% of Treg cells (CD4+CD25+FOXP3+) whereas the addition of 100 nM atRA increased the yield of Treg cells to 66% (p = 0.0088). The addition of RAPA did not increase the number of Treg cells in any of these settings. Treg cells generated in the presence of atRA had an increased expression of the β7 integrin to nearly 100% of the generated Treg cells, while RAPA treated cells showed enhanced expression of CXCR4. The differential expression of homing molecules highlights the possibility of inducing Treg cells with differential organ-specific homing properties. Neither atRA nor RAPA had an effect on the highly methylated CNS2 sites, supporting reports that their contribution to the lineage stability of Treg cells is not mediated by methylation changes in this locus. Treg cells generated in the presence of RAPA show the most potent suppression effect on the proliferation of effector cells.Ítem Synthesis, physicochemical and photophysical characterization of 4-(1-Pyrenyl)-Butyl-α-d-mannopyranoside(Sociedade Brasileira de Química, 2016-02) Sandoval, C.; Arriagada, F.S.; De La Fuente, J.R.; Sanchez, S.A.; Morales, J.; Pizarro, N.; Nonell, S.; Gunther, G.Glycolipids are biomolecules composed of a lipid chain (lipophilic) and a monosaccharide or oligosaccharide as hydrophilic group. Their chemical structure and biological role make them undoubtedly good candidates for a large and continuously growing number of biotechnological applications. Mannose is a carbohydrate present on membrane glycolipids of a wide number of pathogenic microorganisms (bacteria, fungi, protozoa, and viruses) and specifically recognized by several lectins. We synthesized a mannose derivative linked through a short methylene chain to a pyrene moiety which behaves as a surfactant, able to aggregate, and retains the photophysical properties of pyrene: showing comparable absorption and emission spectra, having lower fluorescence quantum yield and the ability to form excimer, and finally the ability to produce O-2((1)Delta(g)) with high quantum yields. Thus, this novel molecule would open future applications for detection (fluorescence) or inactivation (singlet oxygen) of bacterial pathogens, viruses, tumor cells, or particular cells.