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Interferon-ß regulates the production of IL-10 by toll-like receptor-activated ...
Silva, Diogo Pinto Lobo Jesus; Carriche, Guilhermina M.; Castro, António G.; Roque, Susana; Saraiva, MargaridaPattern recognition receptors, such as toll-like receptors (TLRs), perceive tissue alterations and initiate local innate immune responses. Microglia, the resident macrophages of the brain, encode TLRs which primary role is to protect the tissue integrity. However, deregulated activation of TLRs in microglia may lead to chronic neurodegeneration. This double role of microglial responses is often reported in immu...
Cholesteryl hemiesters alter lysosome structure and function and induce proinfl...
Domingues, Neuza; Estronca, Luís M.B.B.; Silva, João; Encarnação, Marisa R.; Mateus, Rita; Silva, Diogo Pinto Lobo Jesus; Santarino, Inês B.Rationale: Cholesteryl hemiesters are oxidation products of polyunsaturated fatty acid esters of cholesterol. Their oxo-ester precursors have been identified as important components of the "core aldehydes" of human atheromata and in oxidized lipoproteins (Ox-LDL). We had previously shown, for the first time, that a single compound of this family, cholesteryl hemisuccinate (ChS), is sufficient to cause irreversi...
Balancing the immune response in the brain: IL-10 and its regulation
Silva, Diogo Pinto Lobo Jesus; Carriche, Guilhermina M.; Saraiva, Margarida; Castro, António G.; Roque, SusanaBackground: The inflammatory response is critical to fight insults, such as pathogen invasion or tissue damage, but if not resolved often becomes detrimental to the host. A growing body of evidence places non-resolved inflammation at the core of various pathologies, from cancer to neurodegenerative diseases. It is therefore not surprising that the immune system has evolved several regulatory mechanisms to achie...
Molecular mechanisms regulating IL-10 expression by microglia upon TLR activation
Silva, Diogo Pinto Lobo JesusMicroglia detect environmental abnormalities, mainly by recognizing exogenous and endogenous danger signals, through pattern recognition receptors (PRRs), such as toll-like receptors (TLRs). Despite the beneficial role of microglia activation towards brain protection against infection or injury, over-activation of these cells has been related to several neurodegenerative disorders, including Alzheimer’s and Par...