<i>Artemisia</i> Extract Suppresses NLRP3 and AIM2 Inflammasome Activation by Inhibition of ASC Phosphorylation

Kwak, Sang-Min; Koppula, Sushruta; In, Eun-Jung; Sun, Xiao; Kim, Young-Kyu; Kim, Myong-Ki; Lee, Kwang-Ho; Kang, Tae-Bong

doi:10.1155/2018/6054069

Cited by 24 publications

(21 citation statements)

References 41 publications

(50 reference statements)

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“…Purinergic receptor blockers, ASC inhibitors, diarylsulphonylurea inhibitors, β-sulfonyl nitrile compounds, and caspase-1 blockers are the broad categories of recently developed NLRP3 inhibitors (170, 171). The most studied compound, MCC950 is a diarylsulphonylurea inhibitor, a potent anti-inflammatory drug and a facilitator of β amyloid clearance in AD animal models (172).…”

Section: Inflammasome Inhibitorsmentioning

confidence: 99%

Rusty Microglia: Trainers of Innate Immunity in Alzheimer's Disease

et al. 2018

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Alzheimer's disease, the most common form of dementia, is marked by progressive cognitive and functional impairment believed to reflect synaptic and neuronal loss. Recent preclinical data suggests that lipopolysaccharide (LPS)-activated microglia may contribute to the elimination of viable neurons and synapses by promoting a neurotoxic astrocytic phenotype, defined as A1. The innate immune cells, including microglia and astrocytes, can either facilitate or inhibit neuroinflammation in response to peripherally applied inflammatory stimuli, such as LPS. Depending on previous antigen encounters, these cells can assume activated (trained) or silenced (tolerized) phenotypes, augmenting or lowering inflammation. Iron, reactive oxygen species (ROS), and LPS, the cell wall component of gram-negative bacteria, are microglial activators, but only the latter can trigger immune tolerization. In Alzheimer's disease, tolerization may be impaired as elevated LPS levels, reported in this condition, fail to lower neuroinflammation. Iron is closely linked to immunity as it plays a key role in immune cells proliferation and maturation, but it is also indispensable to pathogens and malignancies which compete for its capture. Danger signals, including LPS, induce intracellular iron sequestration in innate immune cells to withhold it from pathogens. However, excess cytosolic iron increases the risk of inflammasomes' activation, microglial training and neuroinflammation. Moreover, it was suggested that free iron can awaken the dormant central nervous system (CNS) LPS-shedding microbes, engendering prolonged neuroinflammation that may override immune tolerization, triggering autoimmunity. In this review, we focus on iron-related innate immune pathology in Alzheimer's disease and discuss potential immunotherapeutic agents for microglial de-escalation along with possible delivery vehicles for these compounds.

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Section: Inflammasome Inhibitorsmentioning

confidence: 99%

Rusty Microglia: Trainers of Innate Immunity in Alzheimer's Disease

et al. 2018

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“…Many ASC molecular events related to inflammasome activation have been reported [55]. The adapter protein ASC is essential for both NLRP3 and AIM2 inflammasome formation [56,57].…”

Section: Discussionmentioning

confidence: 99%

“…The adapter protein ASC is essential for both NLRP3 and AIM2 inflammasome formation [56,57]. Therefore, investigation of ASC oligomerization is regarded as a hallmark of inflammasome formation [55]. In a previous study, Artemisia princeps extract (APO) inhibited ASC oligomerization triggered by ATP-, silica-, or nigericin-induced NLRP3 inflammasomes and poly (dA:dT)-induced AIM2 inflammasome activation [55].…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, investigation of ASC oligomerization is regarded as a hallmark of inflammasome formation [55]. In a previous study, Artemisia princeps extract (APO) inhibited ASC oligomerization triggered by ATP-, silica-, or nigericin-induced NLRP3 inflammasomes and poly (dA:dT)-induced AIM2 inflammasome activation [55]. Consistent with that study, our results indicate that the ASC oligomerization was increased in the LPS-primed BMDMs activated by ATP and was dose-dependently inhibited by TCMD ( Figure 4).…”

Section: Discussionmentioning

confidence: 99%

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Tendril extract of Cucurbita moschata suppresses NLRP3 inflammasome activation in murine macrophages and human trophoblast cells

Park

Lee

et al. 2020

Int. J. Med. Sci.

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Inflammation is the root cause of many diseases that pose a serious threat to human health. Excessive inflammation can also result in preterm birth or miscarriage in pregnant women. Pumpkin (Cucurbita moschata Duchesne, CMD) is a well-known traditional health food and medicinal herb used in many countries to treat diabetes, obesity, osteoporosis, cancer and other diseases. In this study, we investigated the effects of hot water extract derived from the tendrils of C. moschata Duchesne (TCMD) on NLRP3 inflammasome activation in murine macrophages and human trophoblast cells. The TCMD treatment of LPS-primed bone marrow-derived macrophages (BMDMs) and human trophoblast cells attenuated NLRP3 inflammasome activation induced by inflammasome activators such as ATP, nigericin, and monosodium urate (MSU). TCMD treatment suppressed IL-1β secretion in a dose-dependent manner, without affecting IL-6 secretion. In addition, TCMD inhibited NLRP3-dependent pyroptosis in BMDMs. TCMD also suppressed the release of mature IL-1β and activation of cleaved-caspase-1 via limited ASC oligomerization. Furthermore, TCMD significantly inhibited IL-1β secretion and pyroptotic cell death in human trophoblast cells. These results suggest that TCMD exhibits anti-inflammatory effects mediated via inhibition of NLRP3 inflammasome activation suggesting therapeutic potential against inflammatory diseases, preterm birth, and miscarriage.

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“…Interestingly efforts are made in order to develop new agents capable to inhibit NLRP3 function. In this regard, old drugs or medications coming from traditional Chinese medicine have been recently found to inhibit NLRP3 inflammasome [ [85] , [86] , [87] , [88] ].…”

Section: Inflammasomopathies/monogenic Recurrent Feversmentioning

confidence: 99%

Periodic fever syndromes and the autoinflammatory diseases (AIDs)

Marino

Tirelli

Giani

et al. 2020

Journal of Translational Autoimmunity

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Innate immune system represents the ancestral defense against infectious agents preserved along the evolution and species; it is phylogenetically older than the adaptive immune system, which exists only in the vertebrates. Cells with phagocytic activity such as neutrophils, macrophages, and natural killer (NK) cells play a key role in innate immunity. In 1999 Kastner et al. first introduced the term “autoinflammation” describing two diseases characterized by recurrent episodes of systemic inflammation without any identifiable infectious trigger: Familial Mediterranean Fever (FMF) and TNF Receptor Associated Periodic Syndrome (TRAPS). Autoinflammatory diseases (AIDs) are caused by self-directed inflammation due to an alteration of innate immunity leading to systemic inflammatory attacks typically in an on/off mode. In addition to inflammasomopathies, nuclear factor (NF)-κB-mediated disorders (also known as Rhelopathies) and type 1 interferonopathies are subjects of more recent studies. This review aims to provide an overview of the field with the most recent updates (see “Most recent developments in..” paragraphs) and a description of the newly identified AIDs.

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Artemisia Extract Suppresses NLRP3 and AIM2 Inflammasome Activation by Inhibition of ASC Phosphorylation

Cited by 24 publications

References 41 publications

Rusty Microglia: Trainers of Innate Immunity in Alzheimer's Disease

Rusty Microglia: Trainers of Innate Immunity in Alzheimer's Disease

Tendril extract of Cucurbita moschata suppresses NLRP3 inflammasome activation in murine macrophages and human trophoblast cells

Periodic fever syndromes and the autoinflammatory diseases (AIDs)

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