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Article Evaluation - Inflammasome
Article and talk page states it needs citations for secondary sources (only 3 included) because there are too many references from primary sources. The "History" section should be added to with papers. The page could also use more citations for some information included. Links checked all worked. Talk page suggests intro is a bit too confusing.

I plan to add to the history section as well as clean up the introduction. With my new sources, I plan to add citations to statements on the page that have no citation. I have found a few sources thus far: "Duncan JA, Canna SW. The NLRC4 Inflammasome. Immunol Rev. 2018;281:115–123. https://doi.org/10.1111/imr.12607""Kawano, Y., Petkau, G., Wolf, I., Tornack, J. and Melchers, F. (2017), IL-7 and immobilized Kit-ligand stimulate serum- and stromal cell-free cultures of precursor B-cell lines and clones. Eur. J.""Xiao, M. (n.d.). The Role of Proinflammatory Cytokine Interleukin-18 in Radiation Injury. Health Physics : Official Journal of the Health Physics Society., 111(2), 212-217.""Shin, Jung-min, Dae-kyoung Choi, Kyung-cheol Sohn, Soo-yeon Kim, Jeong Min Ha, Young Ho Lee, Myung Im, et al. 'Double-Stranded RNA Induces Inflammation Via the NF-Kappa]B Pathway and Inflammasome Activation in the Outer Root Sheath Cells of Hair Follicles.' Scientific Reports (Nature Publisher Group) 7, (03, 2017): 44127. doi: http://dx.doi.org/10.1038/srep44127 . http://ezproxy.carleton.edu/login?url=https://search.proquest.com/docview/1903362508?accountid=9892.""Michael G. Kattah, Barbara A. Malynn, Averil Ma, Ubiquitin-Modifying Enzymes and Regulation of the Inflammasome, Journal of Molecular Biology, Volume 429, Issue 22, 2017, Pages 3471-3485, ISSN 0022-2836, https://doi.org/10.1016/j.jmb.2017.10.001. ( http://www.sciencedirect.com/science/article/pii/S0022283617304710 )"Page Edits (in italics):

Minor edits/additions to:

(lead section)

The inflammasome is a multiprotein oligomer responsible for the activation of inflammatory responses. The inflammasome promotes the maturation and secretion of pro-inflammatory cytokines Interleukin 1β (IL-1β) and Interleukin 18 (IL-18). The secretion of these cytokines results in pyroptosis, a form of programmed pro-inflammatory cell death distinct from apoptosis. In the case of dysregulation of the inflammasome, an assortment of major diseases may arise. It is expressed in myeloid cells and is a component of the innate immune system. The inflammasome complex can consist of caspase 1, PYCARD, NALP and sometimes caspase 5 (also known as caspase 11 or ICH-3). NLRs (nucleotide-binding oligomerization domain and leucine-rich repeat-containing receptors) and ALRs (AIM2-like receptors) can also form an inflammasome. The exact composition of an inflammasome depends on the activator which initiates inflammasome assembly, e.g. dsRNA will trigger one inflammasome composition whereas asbestos will assemble a different variant. Because the pro-inflammatory pathway does not need Toll-like receptors (TLRs), inflammasomes with AIM2 can detect cytoplasmic DNA, a danger signal, that may be threatening and strengthen their innate response.

History
The inflammasome was discovered by the team of Dr. 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. They found that a variety of danger signals could provoke a response from an inflammasome including viral DNA, muramyl dipeptide (MDP), asbestos, and silica. Tschopp and his colleagues found a connection between metabolic syndrome and NLRP3, a subset type of inflammasome. Within their research on NLRP3, they were able to show that when NLRP3 is inhibited, an immunosuppressive behavior of type I interferon was exhibited. Ultimately, the work of Dr. Tschopp and his team led to the research and eventual treatments of many major diseases and ailments.

NLR-subset inflammasomes
NLRP1, NLRP3 and NLRC4 are subsets of the NLR family and thus have two common features: the first is a nucleotide-binding domain (NBD) which is bound by ribonucleotide-phosphates (rNTP) and is important for self-oligomerization. The second is a C-terminus leucine-rich repeat (LRR), which serves as a ligand-recognition domain for other receptors (e.g. TLR) or microbial ligands. NLRP1 has been found in neurons, while both NLRP3 and IPAF/NLRC4 have been identified in microglial cells.

Structure
NLRC4 (also known as IPAF) is the only known subset of the NLRC family to form an inflammasome and contains only a CARD domain in addition to the NBD and LRR, which it uses to recruit procaspase-1 directly.

Activation
NLRC4 is involved in host defense. NLRC4 is activated by bacteria, a number of which have been identified using murine macrophage culture studies: Salmonella typhimurium, Legionella pneumophila and Pseudomonas aeruginosa. The activation process by these bacteria is unclear but is thought to require a type 3 or type 4 secretion system provided by bacterial flagellin, which gains entry through the cell membrane and is then detected by NLRC4, activating it. ASC is required for activation of this inflammasome in some instances.

Palmitate has been shown experimentally to induce the NLRC4 inflammasome without any bacteria present. This may give insight to other functions the inflammasome may have in the immune system, and also suggests that the inflammasome can respond to more than just bacteria. The NLRC4 inflammasome is regulated by cyclic adenosine monophosphate (cAMP).

The adaptor ASC

Apoptosis-associated speck like protein containing a caspase recruitment domain (ASC or Pycard) plays a key role in activation of the inflammasome. ASC helps recruit caspase-1 to associate with NLRs in the inflammasome complex.

ASC also has duties independent of the inflammasome as it has been shown to be required for MHC class II to present antigenic peptides in dendritic cells.

Deregulated Inflammasome Activity

Problems with regulating inflammasomes have been linked to several autoimmune diseases such as type I and type II diabetes, inflammatory bowel disease (IBD), gouty arthritis, multiple sclerosis, and vitiligo as well as auto-inflammatory disorders. These diseases and disorders have been connected to too much or too little secretion of the pro-inflammatory cytokines that the inflammasome is responsible for. Mutations or mistakes by the adaptive immune system (mistaking self as foreign/a danger signal) may be to blame for the dysregulation of the inflammasome.