The NLRP3 inflammasome in health and disease: the good, the bad and the ugly
P Menu,James E Vince +1 more
TLDR
Recently, inflammasome function has been implicated in more common human conditions, which 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 inflammaome activity.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.read more
Citations
More filters
Journal ArticleDOI
Megalin/cubulin-lysosome-mediated albumin reabsorption is involved in the tubular cell activation of NLRP3 inflammasome and tubulointerstitial inflammation
Dan Liu,Yi Wen,Tao-Tao Tang,Lin-Li Lv,Ri-Ning Tang,Hong Liu,Kun-Ling Ma,Steve D. Crowley,Bi-Cheng Liu +8 more
TL;DR: The findings suggest that megalin/cubilin and lysosome rupture are involved in albumin-triggered tubular injury and TI, and implicates the active control of albuminuria as a critical strategy to halt the progression of CKD.
Journal ArticleDOI
Blockage of the NLRP3 inflammasome by MCC950 improves anti-tumor immune responses in head and neck squamous cell carcinoma
Lei Chen,Cong-Fa Huang,Yi-Cun Li,Wei-Wei Deng,Liang Mao,Lei Wu,Wen-Feng Zhang,Lu Zhang,Zhi-Jun Sun +8 more
TL;DR: The results demonstrate that the NLRP3 inflammasome/IL-1β pathway promotes tumorigenesis in HNSCC and inactivation of this pathway delays tumor growth, accompanied by decreased immunosuppressive cell accumulation and an increased number of effector T cells.
Journal ArticleDOI
A Role for the Inflammasome in Spontaneous Labor at Term.
Roberto Romero,Yi Xu,Yi Xu,Olesya Plazyo,Olesya Plazyo,Piya Chaemsaithong,Piya Chaemsaithong,Tinnakorn Chaiworapongsa,Tinnakorn Chaiworapongsa,Ronald Unkel,Ronald Unkel,Nandor Gabor Than,Po Jen Chiang,Zhong Dong,Zhong Dong,Zhonghui Xu,Zhonghui Xu,Adi L. Tarca,Adi L. Tarca,Vikki M. Abrahams,Sonia S. Hassan,Sonia S. Hassan,Lami Yeo,Lami Yeo,Nardhy Gomez-Lopez,Nardhy Gomez-Lopez +25 more
TL;DR: The aims of this study were to determine the expression of major inflammasome components in the chorioamniotic membranes in spontaneous labor at term and whether these events are associated with the release of the mature forms of IL‐1β and IL‐18.
Journal ArticleDOI
NLRP3 Inflammasome: Activation and Regulation in Age-Related Macular Degeneration
TL;DR: The classic model of inflammasome activation is reviewed, the potentials of AMD-related factors to activate the inflammaome in both nonocular immune cells and RPE cells are discussed, and several novel mechanisms for regulating the infammasome activity are introduced.
Journal ArticleDOI
Activation of the Nlrp3 inflammasome by mitochondrial reactive oxygen species: a novel mechanism of albumin-induced tubulointerstitial inflammation.
Dan Liu,Min Xu,Li-Hong Ding,Lin-Li Lv,Hong Liu,Kun-Ling Ma,Ai-Hua Zhang,Steven D. Crowley,Bi-Cheng Liu +8 more
TL;DR: It is demonstrated that albuminuria may serve as an endogenous danger-associated molecular pattern (DAMP) that stimulates TIF via the mROS-mediated activation of the cytoplasmic Nlrp3 inflammasome.
References
More filters
Journal ArticleDOI
Global cancer statistics
TL;DR: A substantial proportion of the worldwide burden of cancer could be prevented through the application of existing cancer control knowledge and by implementing programs for tobacco control, vaccination, and early detection and treatment, as well as public health campaigns promoting physical activity and a healthier dietary intake.
Journal ArticleDOI
Global cancer statistics, 2002.
TL;DR: There are striking variations in the risk of different cancers by geographic area, most of the international variation is due to exposure to known or suspected risk factors related to lifestyle or environment, and provides a clear challenge to prevention.
Journal ArticleDOI
Inflammation and cancer: back to Virchow?
TL;DR: A rationale for the use of cytokine and chemokine blockade, and further investigation of non-steroidal anti-inflammatory drugs, in the chemoprevention and treatment of malignant diseases is provided.
Journal ArticleDOI
The inflammasome: a molecular platform triggering activation of inflammatory caspases and processing of proIL-beta.
TL;DR: In this article, the inflammasome is identified as a caspase-activating complex that comprises caspases-1, casp-5, Pycard/Asc, and NALP1, a Pyrin domain-containing protein sharing structural homology with NODs.
Journal ArticleDOI
Gout-associated uric acid crystals activate the NALP3 inflammasome
TL;DR: 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.