The NLRP3 inflammasome in health and disease: the good, the bad and the ugly

Abstract

While interleukin (IL)-1β plays an important role in combating the invading pathogen as part of the innate immune response, its dysregulation is responsible for a number of autoinflammatory disorders. Large IL-1β activating platforms, known as inflammasomes, can assemble in response to the detection of endogenous host and pathogen-associated danger molecules. Formation of these protein complexes results in the autocatalysis and activation of caspase-1, which processes precursor IL-1β into its secreted biologically active form. Inflammasome and IL-1β activity is required to efficiently control viral, bacterial and fungal pathogen infections. Conversely, excess IL-1β activity contributes to human disease, and its inhibition has proved therapeutically beneficial in the treatment of a spectrum of serious, yet relatively rare, heritable inflammasomopathies. Recently, inflammasome function has been implicated in more common human conditions, such as gout, type II diabetes and cancer. This raises the possibility that anti-IL-1 therapeutics may have broader applications than anticipated previously, and may be utilized across diverse disease states that are linked insidiously through unwanted or heightened inflammasome activity.

Aloe vera downregulates LPS-induced inflammatory cytokine production and expression of NLRP3 inflammasome in human macrophages

“…Production of IL-1␤ strongly depends on the function of multiprotein complexes called inflammasomes. Among inflammasomes, one of the most intensively studied ones is the Nlrp3 inflammasome that contains an Nlrp3 sensor, an ASC adaptor and a caspase-1 enzyme (Cassel et al, 2009;De Nardo and Latz, 2011;Menu and Vince, 2011). Due to its critical function in inflammatory responses, and as part of the safety feature of the immune system, IL-1␤ production is regulated at various levels and requires distinct signals.…”

Molecular mechanisms regulating NLRP3 inflammasome activation

“…[10][11][12] Evidence supports that the aberrant activation of the NLRP3 inflammasome is associated with the pathogenesis of various autoinflammatory, autoimmune, and chronic inflammatory and metabolic diseases, including gout, atherosclerosis, and type 2 diabetes. [13][14][15] Thus, activation of the NLRP3 inflammasome should be tightly regulated to prevent unwanted host damage and excessive inflammation. To date, several regulatory mechanisms and binding partners have been described in NLRP3 inflammasome activation.…”

Naoxintong attenuates Ischaemia/reperfusion Injury through inhibiting NLRP3 inflammasome activation

“…Previous studies demonstrated that inflammation plays a key role in the pathophysiology of myocardial I/R injury 1, 3. Increasing evidence also indicates that a sterile inflammatory response triggered by tissue damage is mediated through a multiple‐protein complex called the inflammasome 4, 5. It is known that nucleotide‐binding oligomerization domain‐Like Receptor with a Pyrin domain 3 (NLRP3) inflammasome are formed after myocardial I/R injury and the subsequent activation process could lead to the interleukin‐1β production 6, 7, which crucially contributes to cardiac ischaemia injury and post‐infarct remodelling.…”