Primer: inflammasomes and interleukin 1β in inflammatory disorders

  title={Primer: inflammasomes and interleukin 1$\beta$ in inflammatory disorders},
  author={Leigh D. Church and Graham P. Cook and Michael F. McDermott},
  journal={Nature Clinical Practice Rheumatology},
Inflammasomes are large, multimeric protein complexes that link the sensing of microbial products and metabolic stress to the proteolytic processing of prointerleukin (pro-IL)-1β to its active form. NALP1 and NALP2 are founding members of the Nod-like receptor family. Other Nod-like receptors, including NALP3 and NOD2, which are associated with inflammatory disorders, have also been described. The NALP1 and NALP3 inflammasomes are located in the cytoplasm and can, therefore, detect… 

Carbon monoxide negatively regulates NLRP3 inflammasome activation in macrophages.

The results suggest that CO negatively regulates NLRP3 inflammasome activation by preventing mitochondrial dysfunction and the inhibitory effect of CO on the translocation of mitochondrial DNA into the cytosol was associated with suppression of cytokine secretion.

Activation and Regulation of NLRP3 by Sterile and Infectious Insults

The existing knowledge about the mechanism of activation of NLRP3 and its regulation during activation by infectious and sterile triggers is summarized.

The inflammasome, an innate immunity guardian, participates in skin urticarial reactions and contact hypersensitivity.

The findings that the inflammasome also plays a role in contact hypersensitivity, and that IL-18, another cytokine involved with inflammaome-activation of caspase-1, may be a major player in dermatitis development, relate to the findings of cellular mechanisms of urticarial rash in CAPS.

Inflammasomes and inflammatory caspases in skin inflammation

In conclusion, inflammasomes and inflammatory caspases are identified as potential inducers and regulators of skin inflammation in contact hypersensitivity and psoriasis and are suggested to bridge the innate immune responses to the adaptive immune system.

ATP Activation of the NLRP2 Inflammasome in Human Astrocytes

The expression of the NLR protein 2 (NLRP2) inflammasome in cortical human astrocytes in vitro is investigated and whether ATP activates the NLRP2 inflammaome is evaluated, suggesting it may be an important component of the CNS inflammatory response and a therapeutic target to inhibit inflammation induced by CNS injury.

Immunomodulatory Effects of Diterpenes and Their Derivatives Through NLRP3 Inflammasome Pathway: A Review

In conclusion, diterpenes and their derivatives could be one of the promising compounds for the treatment of NLRP3-mediated inflammatory diseases and disorders.

Dysfunctional inflammasome in Schnitzler's syndrome.

Findings reveal the presence of an overall derangement of the inflammasome and IL-1beta processing and release in SS.

Cancer, Inflammasomes, and Adjuvanticity

The activation of the NLRP3 inflammasome was recently shown to be instrumental in the initiation of an immune anticancer response that was required for the success of chemotherapy.



Bacterial RNA and small antiviral compounds activate caspase-1 through cryopyrin/Nalp3

A critical role for cryopyrin in host defence through bacterial RNA-mediated activation of caspase-1 is revealed and insights regarding the pathogenesis of autoinflammatory syndromes are provided.

Cryopyrin activates the inflammasome in response to toxins and ATP

It is shown that cryopyrin-deficient macrophages cannot activate caspase-1 in response to Toll-like receptor agonists plus ATP, the latter activating the P2X7 receptor to decrease intracellular K+ levels.

Activation of the IL-1beta-processing inflammasome is involved in contact hypersensitivity.

It is shown that key components of the inflammasome are present in human keratinocytes and that CS like trinitro-chlorobenzene induce caspase-1/ASC dependent IL-1beta and IL-18 processing and secretion, and that ASC- and NALP3-deficient mice display an impaired response to CS.

Activation of the NALP3 inflammasome is triggered by low intracellular potassium concentration

Evidence is provided that activation of NALP3, but not of the IPAF inflammasome, is blocked by inhibiting K+ efflux from cells, suggesting that low intracellular K+ may be the least common trigger of NalP-inflammasomes activation.

Inflammasome adaptors and sensors: intracellular regulators of infection and inflammation

It is shown that the inflammasome is a dynamic entity that is assembled from different adaptors in a stimulus-dependent manner in response to various bacterial pathogens and tissue damage.

The systemic autoinflammatory diseases: inborn errors of the innate immune system.

The current state of the art with regard to the diagnosis, pathogenesis, and treatment of these inborn errors of the innate immune system is summarized.

Gout-associated uric acid crystals activate the NALP3 inflammasome

It is shown that MSU and CPPD engage the caspase-1-activating NALP3 (also called cryopyrin) inflammasome, resulting in the production of active interleukin (IL)-1β and IL-18 in mice deficient in the IL-1β receptor.

Nod-like proteins in immunity, inflammation and disease

An additional key function of Nod-like receptors is in inflammatory conditions, which has been emphasized by the identification of several different mutations in the genes encoding Nod1, Nod2 and NALP3 that are associated with susceptibility to inflammatory disorders.