2024-03-28T09:35:36Zhttp://uvadoc.uva.es/oai/requestoai:uvadoc.uva.es:10324/392122021-06-23T14:07:09Zcom_10324_30605com_10324_894col_10324_41
Regulación de la activación del inflasoma NLRP3 por LIPINA-2 en macrófagos
Lordén Losada, Gema
Balboa García, María Ángeles
Balsinde Rodríguez, Jesús
Universidad de Valladolid. Instituto de Biología y Genética Molecular (IBGM)
Inmunidad innata
2412 Inmunología
2302 Bioquímica
The innate immune system constitutes the first line of defense against invading microbial pathogens, as it can discriminate self from non-self. It can also sense endogenous danger signals that are released from disrupted host tissue or stressed cells. Macrophages, cells of the innate immune system, are able to recognize PAMPs and DAMPs by different receptors that modulate inflammation through transcriptional (TLRs) and post-transcriptional (NLRs) mechanisms. Key players in those pathways are large intracellular multiprotein complexes called inflammasomes. After exposure to pathogens and danger signals, inflammasomes orchestrate innate immune responses through activation of caspase-1 leading to the maturation of pro-inflammatory cytokines pro-IL-1β and pro-IL-18 and an inflammatory form of death known as pyroptosis. NLRP3 inflammasome is the best characterized to date. It is composed of an NLR receptor, the adaptor protein ASC and pro-caspase-1. In macrophages, its activation and assembly need two signals. The first signal, also known as priming, leads to transcription of genes encoding pro-IL-1β and NLRP3 and it is mediated by activation of the transcription factor NF-κB through various receptors, such as TLRs, IL1R or TNFR. The second signal, provided by DAMPs, activates the inflammasome assembly, resulting in the catalytic processing of pro-caspase-1 into its enzymatically active form. NLRP3 inflammasome is activated by a wide range of stimuli, such as bacterial and viral pathogens, pore-forming toxins, lipids, crystals, vaccine adjuvants and stress cellular signals such as ATP. It is broadly agreed that detection of such a diverse variety of agents cannot bind to NLRP3 directly. Instead, it is thought that NLRP3 monitors a common host-derived factor triggered by all these agents. Several hypotheses on molecular mechanisms leading to NLRP3 activation have been formulated. Three models that may not be exclusive are the most widely accepted. The first model suggests that a decrease in intracellular potassium concentration causes inflammasome activation, the second model points at mitochondrial damage and ROS production, and the third model claims that lysosomal destabilization is the mechanism triggering caspase-1 activation.
Departamento de Bioquímica y Biología Molecular y Fisiología
Doctorado en Investigación Biomédica
2019-11-15T12:47:13Z
2019-11-15T12:47:13Z
2016
info:eu-repo/semantics/doctoralThesis
info:eu-repo/semantics/publishedVersion
http://uvadoc.uva.es/handle/10324/39212
10.35376/10324/39212
spa
Attribution-NonCommercial-NoDerivatives 4.0 Internacional
info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc-nd/4.0/
application/pdf
https://uvadoc.uva.es/bitstream/10324/39212/4/Tesis1579-191115.pdf.jpg
Hispana
TEXT
http://creativecommons.org/licenses/by-nc-nd/4.0/
UVaDOC. Repositorio Documental de la Universidad de Valladolid
http://uvadoc.uva.es/handle/10324/39212