What is inflammasomes in health and disease?
Inflammasomes are a group of protein complexes that recognize a diverse set of inflammation-inducing stimuli that include PAMPs and DAMPs and that control the production of important pro-inflammatory cytokines such as interleukin-1β (IL-1β) and IL-18 (refs 4, 5).
What is the function of inflammasomes?
The inflammasomes are innate immune system receptors/sensors that regulate the activation of caspase-1 and induce inflammation in response to infectious microbes and molecules derived from host proteins. It has been implicated in a host of inflammatory disorders.
What is Pyrin structure?
Structure. Pyrin domains are a ~90 amino acid motif present only at the N-terminus of proteins. The core is made of highly conserved hydrophobic residues surrounded by five or six alpha helices with α1→2 linkages. The hydrophobic core allows self-oligomerization into punctate or speck filamentous formations.
How are inflammasomes formed?
Inflammasome formation is triggered by a range of substances that emerge during infections, tissue damage or metabolic imbalances. Once the protein complexes have formed, the inflammasomes activate caspase 1, which proteolytically activates the pro-inflammatory cytokines interleukin-1β (IL-1β)3 and IL-18.
Who discovered inflammasomes?
Jürg Tschopp
The inflammasome was discovered by the team of Jürg Tschopp, at the University of Lausanne, in 2002. Tschopp and team were able to articulate the inflammasome’s role in diseases such as gout and type 2 diabetes.
What is the function of Pyrin domain?
Proteins containing a pyrin domain are frequently involved in programmed cell death processes including pyroptosis and apoptosis. Proteins that possess a pyrin domain interact with the pyrin domains in other proteins to form of multi-protein complexes called inflammasomes and to trigger downstream immune responses.
Where is the MEFV gene?
The MEFV gene is located on the short (p) arm of chromosome 16 at position 13.3, from base pair 3,292,027 to 3,306,626.
How are inflammasomes activated?
Inflammasome activation is initiated by different kinds of cytosolic pattern recognition receptors (PRRs) that respond to either microbe-derived pathogen-associated molecular patterns (PAMPs) or danger-associated molecular patterns (DAMPs) generated by the host cell.
What is the difference between Necroptosis and pyroptosis?
Pyroptosis shares some similarities to necroptosis, but while necroptosis is thought to be a secondary cell death response to situations where apoptosis is inhibited, pyroptosis is generally a primary response to infectious organisms.
What cells make inflammasomes?
Another class of inflammasome assembling PRRs is represented by PYHIN protein family members, such as absent in melanoma 2 (AIM2), which contain HIN200 and pyrin domains10. Inflammasome-assembling PRRs are expressed in many cell types, including macrophages, dendritic cells (DCs), neutrophils, and epithelial cells11.
What does the MEFV gene do?
The MEFV gene provides instructions for making a protein called pyrin (also known as marenostrin). Although pyrin’s function is not fully understood, it likely assists in keeping the inflammation process under control.
What is FMF test?
The Invitae Familial Mediterranean Fever Test analyzes MEFV, the only gene known to cause familial Mediterranean fever (FMF). This test is indicated for any individual in whom a diagnosis of FMF is suspected based on clinical symptoms, laboratory findings, or positive family history.
Where are inflammasomes found?
Inflammasomes are expressed primarily by myeloid cells and are located within the cell. The macromolecular inflammasome structure can be visualized by cryo-electron microscopy. This complex has been found to play a role in a variety of disease models in mice and several have been genetically linked to human diseases.
How is pyroptosis measured?
Subsequent pyroptotic cell lysis is assessed by measuring release of the cytoplasmic enzyme LDH. This technique can be used with many different caspase-1 activating stimuli and provides a rapid (30 min incubation), population-based quantification of cell lysis.
What is necroptotic cell death?
Necroptosis is a programmed form of necrosis, or inflammatory cell death. Conventionally, necrosis is associated with unprogrammed cell death resulting from cellular damage or infiltration by pathogens, in contrast to orderly, programmed cell death via apoptosis.
What is FMF stand for?
Overview. Familial Mediterranean fever (FMF) is a genetic autoinflammatory disorder that causes recurrent fevers and painful inflammation of your abdomen, chest and joints.