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Inflammasomes are multimeric protein complex that assemble in the cytosol upon microbial infection or cellular stress. Upon activation, inflammasomes drive the maturation of proinflammatory cytokines interleukin (IL)-1β and IL-18, and also activate the pore-forming protein gasdermin D to initiate a form of lytic cell death known as 'pyroptosis'. Pannexin-1 is channel-forming glycoprotein that promotes membrane permeability and ATP release during apoptosis; and was implicated in canonical NLRP3 or non-canonical inflammasome activation. Here, by utilising three different pannexin-1 channel inhibitors and two lines of Panx1 macrophages, we provide genetic and pharmacological evidence that pannexin-1 is dispensable for canonical or non-canonical inflammasome activation. Instead, we demonstrate that pannexin-1 cleavage and resulting channel activity during apoptosis promotes NLRP3 inflammasome activation. This article is protected by copyright. All rights reserved.
This article was published in the following journal.
Name: European journal of immunology
Activation of the NLRP3 inflammasome by Leishmania parasites is critical for the outcome of leishmaniasis, a disease that affects millions of people worldwide. We investigate the mechanisms involved i...
ATP acts as a canonical activator to induce NLRP3 (NOD-like receptor family, pyrin domain containing 3) inflammasome activation in macrophages, leading to caspase-1/gasdermin D (GSDMD)-mediated pyropt...
The NLRP3 inflammasome is activated in response to multiple stimuli and triggers activation of caspase-1 (CASP1), IL-1β production, and inflammation. NLRP3 activation requires two signals. The first ...
NLRP3 inflammasome plays a key role in Western diet-induced systemic inflammation and was recently shown to mediate long-lasting trained immunity in myeloid cells. Saturated fatty acids (SFAs) are ste...
Leishmaniasis is a neglected tropical disease affecting millions of individuals worldwide. P2X7 receptor has been linked to the elimination of Leishmania amazonensis. Biological responses evoked by P2...
Activation of caspase-4 and human caspase-5 (orthologs of caspase-11 in mice) in innate immune cells.
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Parkinson disease (PD) is a chronic degenerative disease characterized by a progressive loss of dopaminergic neurons in the substantia nigra. Its pathophysiological mechanisms are still pa...
RAGE (the receptor for advanced glycation end-products) is a marker of alveolar type I cell injury and a pivotal mediator of acute inflammation and innate immunity. RAGE pathway is highly ...
For a few years, there has been a keen interest of clinicians and patients for "lighter" antiretroviral strategies based on two- or even single drug regimens rather than the canonical trip...
A signal transducing adaptor protein that contains an N-terminal CARD DOMAIN and functions in the ADAPTIVE IMMUNE RESPONSE. It promotes PRO-CASPASE-9 maturation and APOPTOSIS, activation of NF-KAPPA B, and is a substrate for MALT1 PARACASPASE.
A proteolytically-cleaved membrane glycoprotein and member of the TNF superfamily that is highly expressed in a variety of tissues including heart, pancreas, brain, and peripheral blood lymphocytes. The secreted extracellular form is a weak inducer of APOPTOSIS for some cell types and a ligand for the FN14 RECEPTOR. It mediates activation of NF-KAPPA-B and promotes ANGIOGENESIS and proliferation of ENDOTHELIAL CELLS, as well as expression of cytokines involved in INFLAMMATION.
A flavoprotein that functions as a powerful antioxidant in the MITOCHONDRIA and promotes APOPTOSIS when released from the mitochondria. In mammalian cells AIF is released in response to pro-apoptotic protein members of the bcl-2 protein family. It translocates to the CELL NUCLEUS and binds DNA to stimulate CASPASE-independent CHROMATIN condensation.
A serine peptidase that contains a C-terminal PDZ domain. It localizes to the mitochondrial membrane and intermembrane space, translocating to the cytoplasm following APOPTOSIS stimuli, such as UV irradiation; it promotes cell death by binding to and inhibiting INHIBITOR OF APOPTOSIS PROTEINS, resulting in an increase in activity of CASPASES. Mutations in the HTRA2 gene are associated with Type 13 PARKINSON DISEASE.
A secreted tumor necrosis factor receptor family member that has specificity for TNF-RELATED APOPTOSIS-INDUCING LIGAND. It plays a modulating role in activation of APOPTOSIS signaling.
Within medicine, nutrition (the study of food and the effect of its components on the body) has many different roles. Appropriate nutrition can help prevent certain diseases, or treat others. In critically ill patients, artificial feeding by tubes need t...
Antiretroviral Therapy Clostridium Difficile Ebola HIV & AIDS Infectious Diseases Influenza Malaria Measles Sepsis Swine Flu Tropical Medicine Tuberculosis Infectious diseases are caused by pathogenic...