A5035722428- Inflammasome and immune disorders
- Heme Oxygenase-1 and Carbon Monoxide
- Neurotransmitter Receptor Influence on Behavior
- Fuzzy Logic and Control Systems
- Neural Networks and Applications
- IL-33, ST2, and ILC Pathways
- Adenosine and Purinergic Signaling
- Immune Response and Inflammation
- Stress Responses and Cortisol
- Gout, Hyperuricemia, Uric Acid
- Receptor Mechanisms and Signaling
- Autoimmune and Inflammatory Disorders Research
- Fuzzy Systems and Optimization
- Pneumonia and Respiratory Infections
- Circadian rhythm and melatonin
- Neonatal Respiratory Health Research
- Neuroscience and Neuropharmacology Research
- Power Quality and Harmonics
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Power Transformer Diagnostics and Insulation
- Immune cells in cancer
- Empathy and Medical Education
- Kawasaki Disease and Coronary Complications
- COVID-19 Impact on Reproduction
- Constraint Satisfaction and Optimization
Universidad de Murcia
1997-2024
Manchester Academic Health Science Centre
2020-2024
University of Manchester
2020-2024
Hospital La Luz
2023
Instituto Murciano de Investigación Biosanitaria
2012-2023
Centre for Inflammation Research
2020
Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas
2014-2018
Universidad de Málaga
2010-2017
Hospital Universitario Virgen de la Arrixaca
2015-2016
Centro de Investigación Biomédica en Red
2015-2016
Interleukin-1β (IL-1β) is a critical regulator of the inflammatory response. IL-1β not secreted through conventional ER–Golgi route protein secretion, and to date its mechanism release has been unknown. Crucially, secretion depends upon processing precursor form following activation multimolecular inflammasome complex. Using novel reversible pharmacological inhibitor process, in combination with biochemical, biophysical, real-time single-cell confocal microscopy macrophage cells expressing...
Abstract Sepsis is characterized by a systemic inflammatory response followed immunosuppression of the host. Metabolic defects and mitochondrial failure are common in immunocompromised patients with sepsis. The NLRP3 inflammasome important for establishing an after activation purinergic P2X7 receptor. Here, we study cohort individuals intra-abdominal origin sepsis show that patient monocytes have impaired Furthermore, most sepsis-related deaths among whose profoundly altered. In from...
The NLRP3 inflammasome is an important regulator of inflammation and immunity. It a multimolecular platform formed within cells that facilitates the activation proinflammatory caspases to drive secretion cytokines such as interleukin-1β (IL-1β). Knowledge mechanisms regulating formation incomplete. Here we report Cl- channel-dependent dynamic ASC oligomers specks remain inactive in absence K+ efflux. Formed after efflux exclusively, are dependent, reversible, inactive, although they further...
Article11 September 2018Open Access Source DataTransparent process USP7 and USP47 deubiquitinases regulate NLRP3 inflammasome activation Pablo Palazón-Riquelme Division of Infection, Immunity Respiratory Medicine, Faculty Biology, Medicine Health, Manchester Collaborative Centre Inflammation Research, Academic Health Science Centre, Core Technology Facility, School Biological Sciences, University Manchester, UK Search for more papers by this author Jonathan D Worboys Jack Green Neuroscience...
Abstract The activation of P2X7 receptor (P2X7R) on M1 polarized macrophages induces the assembly NLRP3 inflammasome leading to release pro-inflammatory cytokines and establishment inflammatory response. However, P2X7R signaling is uncoupled M2 without changes activation. In this study, we analyzed secretome in wild-type P2X7R-deficient either or proved that proteins released after stimulation goes beyond caspase-1 secretome. characterization P2X7R-secretome reveals a new function through...
In most seasons, the influenza vaccine is effective in preventing influenza, but it not clear whether equally mild and severe cases. We designed a case-control study to compare effectiveness of outpatient, inpatient, or fatal cases laboratory-confirmed influenza.Hospitalized patients (n = 691) with 2010-2011 season recruited 29 Spanish hospitals were individually matched by age, admission/visit date, province an outpatient control. Severe considered those admitted intensive care units who...
Interleukin (IL)-18 and IL-1β are potent pro-inflammatory cytokines that contribute to inflammatory conditions such as rheumatoid arthritis Alzheimer's disease. They produced inactive precursors activated by large macromolecular complexes called inflammasomes upon sensing damage or pathogenic signals. NLRP3 inflammasome activation is regarded require a priming step causes gene upregulation, also post-translational licencing. A subsequent leads the assembly of complex cleavage pro-IL-18...
Inflammasomes are cytosolic molecular platforms that alert the immune system about presence of infection. Here we report zebrafish guanylate-binding protein 4 (Gbp4), an IFNγ-inducible GTPase harbouring a C-terminal CARD domain, is required for inflammasome-dependent clearance Salmonella Typhimurium (ST) by neutrophils in vivo. Despite Gbp4 requires universal inflammasome adaptor Asc mediating its antibacterial function. In addition, activity indispensable activation and ST clearance....
Abstract Apoptosis-associated speck-like protein containing a C-terminal caspase recruitment domain (ASC) is key adaptor molecule required for the inflammatory processes. ASC acts by bridging NLRP proteins, such as NLRP3, with procaspase-1 within inflammasome complex, which subsequently results in activation of caspase-1 and secretion IL-1β IL-18. In response to bacterial infection, also forms specks self-oligomerization activate induce pyroptosis. Hitherto, role these NLRP3 danger signals,...
Inflammation driven by the NLRP3 inflammasome is coordinated through multiple signaling pathways and regulated subcellular organelles. Here, we tested hypothesis that senses disrupted endosome trafficking to trigger formation inflammatory cytokine secretion. NLRP3-activating stimuli triggered localization of vesicles positive for endolysosomal markers inositol lipid PI4P. Chemical disruption sensitized macrophages activator imiquimod, driving enhanced activation Together, these data suggest...
This paper presents different approaches to the problem of fuzzy rules extraction by using clustering as main tool. Within these we describe six methods that represent alternatives in modeling process and how they can be integrated with a genetic algorithms. These attempt obtain first approximation without any assumption about structure data. Because objective is an approximation, propose must simple possible, but also, have great approximative capacity way work directly sets induced...
Abstract The nucleotide-binding domain and leucine-rich repeat-containing receptor with a pyrin 3 (NLRP3) inflammasome is sensor for different types of infections alterations homeostatic parameters, including abnormally high levels the extracellular nucleotide ATP or crystallization metabolites. All NLRP3 activators trigger similar intracellular pathway, where decrease in K + concentration permeabilization plasma membrane are key steps. Cationic amphipathic antimicrobial peptides peptide...
Signaling through the inflammasome is important for inflammatory response. Low concentrations of intracellular K+ are associated with specific oligomerization and activation NLRP3 inflammasome, a type involved in sterile inflammation. After oligomerization, ASC protein binds forms oligomeric filaments that culminate large complexes named specks. specks also initiated from different scaffolds, such as AIM2, NLRC4, or Pyrin. oligomers recruit caspase-1 then induce its interactions between...
The transcription factor DeltaFosB is induced in the nucleus accumbens (NAc) by drugs of abuse. This study was designed to evaluate possible modifications FosB/DeltaFosB expression both hypothalamic and extrahypothalamic brain stress system during morphine dependence withdrawal. Rats were made dependent on and, day 8, injected with saline or naloxone. Using immunohistochemistry western blot, FosB/DeltaFosB, tyrosine hydroxylase (TH), corticotropin-releasing (CRF) pro-dynorphin (DYN) measured...
Interleukin 1β (IL-1β) plays a major role in inflammation and is secreted by immune cells, such as macrophages, upon recognition of danger signals. Its secretion regulated the inflammasome, assembly which results caspase 1 activation leading to gasdermin D (GSDMD) pore formation IL-1β release. During inflammation, signals also activate complement cascade, resulting membrane attack complex (MAC). Here, we report that stimulation LPS-primed human macrophages with sub-lytic levels MAC NOD-like...
Exposure to drugs of abuse or stress results in adaptation the brain involving changes gene expression and transcription factors. Morphine withdrawal modulates through various second-messenger signal transduction systems. Here, we investigated activation factor, cAMP-response element binding protein (CREB), hypothalamic paraventricular nucleus (PVN) kinases that may mediate morphine withdrawal-triggered CREB response hypothalamic-pituitary-adrenocortical (HPA) axis after naloxone-induced...
Abstract Unconventional protein secretion represents an important process of the inflammatory response. The release pro-inflammatory cytokine interleukin (IL)-1β which burst during pyroptosis as a consequence gasdermin D plasma membrane pore formation, can also occur through other unconventional pathways dependent on caspase-1 activation. However, how mediates independently remains poorly understood. Here we show that following activation by different inflammasomes, cleaves early endosome...
The transcription factor cAMP response element binding protein (CREB) has been implicated in the actions of drugs abuse several brain areas. However, little is known about CREB regulation nucleus tractus solitarius (NTS)-A(2) catecholaminergic cell group, one key regions stress system. Morphine withdrawal modulates gene expression NTS through various second-messenger signal transduction systems including activation extracellular signal-regulated kinases 1/2 (ERK(1/2)) and kinase C (PKC). In...
NLRP3 inflammasome is a multiprotein complex responsible for the activation of inflammatory caspase-1, resulting in processing and release pro-inflammatory cytoquines IL-1β IL-18 (Schroder Tschopp, 2010). This composed sensor protein connected to caspase-1 through adaptor ASC (apoptosis-associated speck-like with caspase-recruitment domain) We others have reported that upon functional oligomeric particles were released from cells, acting as danger signals amplify inflammation by promoting...
Experimental and clinical findings have shown that administration of adrenoceptor antagonists alleviated different aspects drug withdrawal dependence. The present study tested the hypothesis changes in CREB activation phosphorylated TORC1 levels hypothalamic paraventricular nucleus (PVN) after naloxone-precipitated morphine as well HPA axis activity arises from α1- and/or β-adrenoceptor activation. effects dependence on phosphorylation (pCREB), (pTORC1), response were measured by...
Abstract Inflammation driven by the NLRP3 inflammasome is coordinated through multiple signaling pathways and with a poorly defined regulation sub-cellular organelles. Here, we tested hypothesis that senses disrupted endosome trafficking to trigger formation inflammatory cytokine secretion. NLRP3-activating stimuli triggered localization of vesicles positive for markers inositol lipid PtdIns4P. Chemical disruption sensitized macrophages activator imiquimod driving enhanced activation...