Person:
García-Fojeda García-Valdecasas, María Belén

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First Name
María Belén
Last Name
García-Fojeda García-Valdecasas
URI
https://hdl.handle.net/20.500.14352/76061
Affiliation
Universidad Complutense de Madrid
Faculty / Institute
Ciencias Químicas
Department
Bioquímica y Biología Molecular
Area
Bioquímica y Biología Molecular
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2016 - 20172
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Author: Lorenzo, Alba de × Item Type: Publication ×

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    Apoptosis, Toll-like, RIG-I-like and NOD-like Receptors Are Pathways Jointly Induced by Diverse Respiratory Bacterial and Viral Pathogens
    (Frontiers in Immunology, 2017) Martínez, Isidoro ; Oliveros, Juan; Cuesta, Isabel; Barrera, Jorge; Ausina, Vicente; Casals Carro, María Cristina; Lorenzo, Alba de ; García, Ernesto; García-Fojeda García-Valdecasas, María Belén; Garmendia, Junkal ; González-Nicolau, Mar; Lacoma, Alicia; Menéndez, Margarita; Moranta, David ; Nieto, Amelia ; Ortín, Juan; Pérez-González, Alicia ; Prat, Cristina ; Ramos-Sevillano, Elisa ; Regueiro, Verónica; Rodriguez-Frandsen, Ariel ; Solís, Dolores ; Yuste, José ; Bengoechea, José ; Melero, José
    Lower respiratory tract infections are among the top five leading causes of human death. Fighting these infections is therefore a world health priority. Searching for induced alterations in host gene expression shared by several relevant respiratory pathogens represents an alternative to identify new targets for wide-range host-oriented therapeutics. With this aim, alveolar macrophages were independently infected with three unrelated bacterial (Streptococcus pneumoniae, Klebsiella pneumoniae, and Staphylococcus aureus) and two dissimilar viral (respiratory syncytial virus and influenza A virus) respiratory pathogens, all of them highly relevant for human health. Cells were also activated with bacterial lipopolysaccharide (LPS) as a prototypical pathogen-associated molecular pattern. Patterns of differentially expressed cellular genes shared by the indicated pathogens were searched by microarray analysis. Most of the commonly up-regulated host genes were related to the innate immune response and/or apoptosis, with Toll-like, RIG-I-like and NOD-like receptors among the top 10 signaling pathways with over-expressed genes. These results identify new potential broad-spectrum targets to fight the important human infections caused by the bacteria and viruses studied here.
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    Surfactant Protein A Prevents IFN-γ/IFN-γ Receptor Interaction and Attenuates Classical Activation of Human Alveolar Macrophages
    (Journal of Immunology, 2016) Minutti, Carlos; García-Fojeda García-Valdecasas, María Belén; Sáenz, Alejandra ; Casas-Engel, Mateo de las ; Guillamat-Prats, Raquel ; Lorenzo, Alba de ; Serrano-Mollar, Anna ; Corbí, Ängel; Casals Carro, María Cristina
    Lung surfactant protein A (SP-A) plays an important function in modulating inflammation in the lung. However, the exact role of SP-A and the mechanism by which SP-A affects IFN-γ–induced activation of alveolar macrophages (aMϕs) remains unknown. To address these questions, we studied the effect of human SP-A on rat and human aMϕs stimulated with IFN-γ, LPS, and combinations thereof and measured the induction of proinflammatory mediators as well as SP-A’s ability to bind to IFN-γ or IFN-γR1. We found that SP-A inhibited (IFN-γ + LPS)–induced TNF-α, iNOS, and CXCL10 production by rat aMϕs. When rat macrophages were stimulated with LPS and IFN-γ separately, SP-A inhibited both LPS-induced signaling and IFN-γ–elicited STAT1 phosphorylation. SP-A also decreased TNF-α and CXCL10 secretion by ex vivo–cultured human aMϕs and M-CSF–derived macrophages stimulated by either LPS or IFN-γ or both. Hence, SP-A inhibited upregulation of IFN-γ–inducible genes (CXCL10, RARRES3, and ETV7) as well as STAT1 phosphorylation in human M-CSF–derived macrophages. In addition, we found that SP-A bound to human IFN-γ (KD = 11 ± 0.5 nM) in a Ca2+-dependent manner and prevented IFN-γ interaction with IFN-γR1 on human aMϕs. We conclude that SP-A inhibition of (IFN-γ + LPS) stimulation is due to SP-A attenuation of both inflammatory agents and that the binding of SP-A to IFN-γ abrogates IFN-γ effects on human macrophages, suppressing their classical activation and subsequent inflammatory response.