Cellular localization of NLRP3 inflammasome

Wang, Yan; Yang, Chong‐Ren; Mao, Kairui; Chen, Shuzhen; Meng, Guangxun; Sun, Bing

doi:10.1007/s13238-013-2113-2

Cited by 47 publications

(31 citation statements)

References 31 publications

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“…More interestingly, the observations of colocalization of NLRP3 inflammasome with LDs and suppression of IL-1β by LD inhibition imply that E-FABP-mediated LD formation provide a new platform for the effective activation of the inflammasome. Given the unknown cellular localization of inflammasomes and underappreciated functions of LDs (Farese, Jr. and Walther, 2009; Wang et al, 2013), our data suggest a new interaction between inflammasomes and LDs. Thus, E-FABP represents a new molecular link between overnutrition and metabolic inflammation through coupling fatty acid trafficking and inflammasome activation.…”

Section: Discussionmentioning

confidence: 84%

Epidermal Fatty Acid Binding Protein Promotes Skin Inflammation Induced by High-Fat Diet

et al. 2015

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SUMMARY Defining specific cellular and molecular mechanisms in most obesity-related diseases remains an important challenge. Here we report a serendipitous finding that consumption of a high-fat diet (HFD) greatly increased the occurrence of skin lesions in C57BL/6 mice. We demonstrated that HFD induced the accumulation of a specific type of CD11c+ macrophages in skin preceding detectable lesions. These cells primed skin to induce IL-1β and IL-18 signaling, which further promoted the cytokines IFNγ- and IL-17-mediated skin inflammation. Mechanistically, epidermal fatty acid binding protein (E-FABP) was significantly upregulated in skin of obese mice, which coupled lipid droplet formation and NLRP3 inflammasome activation. Deficiency of E-FABP in obese mice decreased recruitment of CD11c+ macrophages in skin tissues, reduced production of IL-1β and IL-18, and consequently dampened activation of effector T cells. Furthermore, E-FABP deficient mice are completely resistant to HFD-induced skin lesions. Collectively, E-FABP represents a molecular sensor triggering HFD-induced skin inflammation.

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Section: Discussionmentioning

confidence: 84%

Epidermal Fatty Acid Binding Protein Promotes Skin Inflammation Induced by High-Fat Diet

et al. 2015

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“…Following these early studies, co‐immunoprecipitation has confirmed NLRP3, ASC, and caspase‐1 oligomerization, but the molecular weight of these NLRP3 complexes remains to be directly assessed. Oligomerization of NLRP3 and ASC in HMW complexes has also been supported by immunofluorescent confocal microscopy studies showing co‐localization of NLRP3 and ASC in specks . However, biochemical determination of the predominant molecular weight of endogenous NLRP3 inflammasome complexes has yet to be determined and will be relevant to assess what constitutes an active inflammasome.…”

Section: Inflammasome Complex Assemblymentioning

confidence: 88%

“…In contrast to these studies supporting mitochondrial or MAM localization of NLRP3 inflammasomes, microscopy experiments by Wang et al . using a variety of organelle markers could not determine a specific localization of ASC specks, and because NLRP3 co‐localizes with the specks, the authors concluded that NLRP3 is cytosolic. However, association of NLRP3 with specific organelles was not independently examined, and as it is unclear whether the ASC speck represents an active NLRP3 inflammasome (discussed below), it is difficult to know whether or how these findings relate to NLRP3 localization.…”

Section: Mitochondrial Damage In Nlrp3 Inflammasome Activationmentioning

confidence: 99%

Initiation and perpetuation of NLRP3 inflammasome activation and assembly

Elliott

Sutterwala

2015

Immunological Reviews

713

561

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Summary The NLRP3 (NOD-like receptor family, pyrin domain containing 3) inflammasome is a multiprotein complex that orchestrates innate immune responses to infection and cell stress through activation of Caspase-1 and maturation of inflammatory cytokines pro-interleukin-1β (pro-IL-1β) and pro-IL-18. Activation of the inflammasome during infection can be protective, but unregulated NLRP3 inflammasome activation in response to non-pathogenic endogenous or exogenous stimuli can lead to unintended pathology. NLRP3 associates with mitochondria and mitochondrial molecules, and activation of the NLRP3 inflammasome in response to diverse stimuli requires cation flux, mitochondrial Ca2+ uptake, and mitochondrial reactive oxygen species accumulation. It remains uncertain whether NLRP3 surveys mitochondrial integrity and senses mitochondrial damage, or whether mitochondria simply serve as a physical platform for inflammasome assembly. The structure of the active, caspase-1-processing NLRP3 inflammasome also requires further clarification, but recent studies describing the prion-like properties of ASC have advanced the understanding of how inflammasome assembly and caspase-1 activation occur while raising new questions regarding the propagation and resolution of NLRP3 inflammasome activation. Here we review the mechanisms and pathways regulating NLRP3 inflammasome activation, discuss emerging concepts in NLRP3 complex organization, and expose the knowledge gaps hindering a comprehensive understanding of NLRP3 activation.

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“…NLRP3 is expressed in the cytosol of various cell types, including granulocytes, monocytes, macrophages, dendritic cells, T and B cells, epithelial cells, osteoblasts, fibroblasts and melanoma cells . NLRP3 inflammasome is found distributed throughout the cytoplasm rather than within any specific organelles . Activation of NLRP3 leads to the homotypic protein–protein interaction between PYD of NLRP3 and the PYD of ASC.…”

Section: Expression and Activation Of The Nlrp3 Inflammasomementioning

confidence: 99%

The NLRP3 inflammasome: role in airway inflammation

Ammit

2014

Clin Experimental Allergy

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Asthma is characterized by airway inflammation, airway hyperresponsiveness and airway remodelling. Uncontrolled airway inflammation or repeated asthma exacerbations can lead to airway remodelling, which cannot be reversed by current pharmacological treatment, and consequently lead to decline in lung function. Thus, it is critical to understand airway inflammation in asthma and infectious exacerbation. The inflammasome has emerged as playing a key role in innate immunity and inflammation. Upon ligand sensing, inflammasome components assemble and self-oligomerize, leading to caspase-1 activation and maturation of pro-IL-1β and pro-IL-18 into bioactive cytokines. These bioactive cytokines then play a pivotal role in the initiation and amplification of inflammatory processes. In addition to facilitating the proteolytic activation of IL-1β and IL-18, inflammasomes also participate in cell death through caspase-1-mediated pyroptosis. In this review, we describe the structure and function of the inflammasome and provide an overview of our current understanding of role of the inflammasome in airway inflammation. We focus on nucleotide-binding domain and leucine-rich repeat protein 3 (NLRP3) inflammasome as it is the best-characterized subtype shown expressed in airway and considered to play a key role in chronic airway diseases such as asthma.

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Cellular localization of NLRP3 inflammasome

Cited by 47 publications

References 31 publications

Epidermal Fatty Acid Binding Protein Promotes Skin Inflammation Induced by High-Fat Diet

Epidermal Fatty Acid Binding Protein Promotes Skin Inflammation Induced by High-Fat Diet

Initiation and perpetuation of NLRP3 inflammasome activation and assembly

The NLRP3 inflammasome: role in airway inflammation

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