Natural Compounds as Regulators of NLRP3 Inflammasome-Mediated IL-1βProduction

Tőzsér, József; Benkő, Szilvia

doi:10.1155/2016/5460302

Cited by 110 publications

(76 citation statements)

References 128 publications

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“…In support of this, a similar suggestive observation was made with the monoflavonoid quercetin ( 23 ), which was recently confirmed as a direct inhibitor of the NLRP3 inflammasome activation via interference with the oligomerization of the adaptor protein apoptosis-associated speck-like protein containing a CARD ( 70 ). Phytochemicals, such as flavonoids, are typically effective in diseases where IL-1β production and NLRP3 inflammasome activation make part of the pathophysiology, and growing evidence support the action of these compounds on NLRP3 activation ( 71 ). Thus, biflavonoids/monoflavonoids could represent a novel class of small molecule NLRP3 inflammasome inhibitors.…”

Section: Discussionmentioning

confidence: 99%

Natural Biflavonoids Modulate Macrophage–Oxidized LDL Interaction In Vitro and Promote Atheroprotection In Vivo

et al. 2017

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The accumulation of oxidized ApoB-100-containing lipoproteins in the vascular intima and its subsequent recognition by macrophages results in foam cell formation and inflammation, key events during atherosclerosis development. Agents targeting this process are considered potentially atheroprotective. Since natural biflavonoids exert antioxidant and anti-inflammatory effects, we evaluated the atheroprotective effect of biflavonoids obtained from the tropical fruit tree Garcinia madruno. To this end, the pure biflavonoid aglycones morelloflavone (Mo) and volkensiflavone (Vo), as well as the morelloflavone’s glycoside fukugiside (Fu) were tested in vitro in primary macrophages, whereas a biflavonoid fraction with defined composition (85% Mo, 10% Vo, and 5% Amentoflavone) was tested in vitro and in vivo. All biflavonoid preparations were potent reactive oxygen species (ROS) scavengers in the oxygen radical absorbance capacity assay, and most importantly, protected low-density lipoprotein particle from both lipid and protein oxidation. In biflavonoid-treated macrophages, the surface expression of the oxidized LDL (oxLDL) receptor CD36 was significantly lower than in vehicle-treated macrophages. Uptake of fluorescently labeled oxLDL and cholesterol accumulation were also attenuated in biflavonoid-treated macrophages and followed a pattern that paralleled that of CD36 surface expression. Fu and Vo inhibited oxLDL-induced ROS production and interleukin (IL)-6 secretion, respectively, whereas all aglycones, but not the glucoside Fu, inhibited the secretion of one or more of the cytokines IL-1β, IL-12p70, and monocyte chemotactic protein-1 (MCP-1) in lipopolysaccharide (LPS)-stimulated macrophages. Interestingly, in macrophages primed with low-dose LPS and stimulated with cholesterol crystals, IL-1β secretion was significantly and comparably inhibited by all biflavonoid preparations. Intraperitoneal administration of the defined biflavonoid fraction into ApoE−/− mice was atheroprotective, as evidenced by the reduction of the atheromatous lesion size and the density of T cells and macrophages infiltrating the aortic root; moreover, this treatment also lowered the circulating levels of cholesterol and the lipid peroxidation product malondialdehyde. These results reveal the potent atheroprotective effects exerted by biflavonoids on key events of the oxLDL–macrophage interphase: (i) atheroligand formation, (ii) atheroreceptor expression, (iii) foam cell transformation, and (iv) prooxidant/proinflammatory macrophage response. Furthermore, our results also evidence the antioxidant, anti-inflammatory, hypolipemiant, and atheroprotective effects of Garcinia madruno’s biflavonoids in vivo.

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Section: Discussionmentioning

confidence: 99%

Natural Biflavonoids Modulate Macrophage–Oxidized LDL Interaction In Vitro and Promote Atheroprotection In Vivo

et al. 2017

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“…Antioxidants are known to impact the NLRP inflammasome. 49,50 Of special interest were extracts of L. erythrorhizon roots, H. pluvialis algae, C. sinensis leaf and Glycyrrhiza glabra root which are known to show anti-inflammatory effects on skin or skin cells. [51][52][53][54] All four antioxidants are commercially available as oil-soluble extracts and were blended to provide a fully soluble and Citrus sinensis fruit was examined using both UV and ATP activation, Figures 8 and 9.…”

Section: Treatment With Oil-soluble Antioxidantbased Blend With Uvb Amentioning

confidence: 99%

In vitro expression of NLRP inflammasome-induced active Caspase-1 expression in normal human epidermal keratinocytes (NHEK) by various exogenous threats and subsequent inhibition by naturally derived ingredient blends

Gruber¹,

Holtz²

2019

JIR

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Background: The discovery of the nod-like receptor protein (NLRP) inflammasomes in 2002 has led to the rapid identification of these unique cellular proteins as key targets for studies on innate inflammation pathways. The NLRP inflammasomes have been shown to be expressed in normal human epidermal keratinocytes (NHEK) and human dermal fibroblasts (HDF). NLRP inflammasomes in keratinocytes are interesting as these skin cells are the first living cells in the skin to contact external exogenous threats such as UV energy, chemicals, physical trauma, and bacteria and viruses. Activation of the NLRP Inflammasomes by exogenous threats results in the release of active Caspase-1 (ACasp-1), a key protease enzyme, which targets inactive forms of IL-1β, IL-18 as well as IL-1α and IL-33. Purpose: This article discusses efforts to examine the release of active Caspase-1 from NHEKs activated by various exogenous threats including UVB energy, ATP, Nigericin and Urban Dust. The work further examines if, after inflammasome activation and Caspase-1 release, certain naturally derived botanical ingredients known to have anti-inflammatory effects can function to inhibit upregulation of active Caspase-1. Methods: NHEK were treated with various doses of UVB, ATP and Nigericin and with a single dose of Urban Dust. ACasp-1 expression was measured after 3 and 20 hours using the Promega Caspase Glo-1 bioluminescent assay. After confirmation that 60 mJ/cm 2 of UVB and 5mM of ATP were effective to activate NHEK ACasp-1 release after 20 hrs, these conditions were employed to examine the influence of three botanical blends of ingredients on their ability to inhibit ACasp-1 expression. Results: Initial results demonstrate that NHEKs can be activated to release active Caspase-1 by ATP and UVB, but not by Nigericin or Urban Dust. In addition, it was unexpectedly found that, while ATP and UVB activated NHEKs, the release of ACasp-1-did not happen within the first 3 hours after exposure but did become significant after 20 hours. Additional results indicate that a blend of polysaccharides and two blends of antioxidants, one oilsoluble and the other water-soluble, known for their anti-inflammatory effects, can reduce expression of active Caspase-1 in activated NHEKs when applied extracellularly. Conclusion: Expression of NLRP activated release of ACasp-1 was found to be influenced by UVB and ATP but not by Nigericin or Urban Dust. The effects were also time dependent. Several botanical extract blends were found to reduce ACasp-1 expression in previously activated NHEKs. Links between these inflammatory effects and processes of cellular inflammaging are discussed.

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“…Latz, Xiao, and Stutz () reported that NLRP3 inflammasome not only activated the secretion of IL‐1β, but also promoted recruitment of other immune cells. Upon activation by various types of endogenous or exogenous stimuli, NLRP3 inflammasome leads to cleavage of pro‐caspase‐1 into the active form, which subsequently promotes the release of mature IL‐β (Abderrazak et al, ; Latz et al, ; Tőzsér & Benkő, ). During the development of RR, adverse stimuli might stimulate the polarization of M1 macrophages and their IL‐1β production by activating NLRP3 inflammasome.…”

Section: Introductionmentioning

confidence: 99%

NLRP3 inflammasome mediates M1 macrophage polarization and IL‐1β production in inflammatory root resorption

Zhang

Liu

Wan

et al. 2020

J Clinic Periodontology

147

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Aims To explore the involvement of NOD‐like receptor protein 3 (NLRP3) inflammasome and M1 macrophage in root resorption (RR). Methods A rat RR model was established by excessive orthodontic force. After different force‐loading time, the expression levels of NLRP3, caspase‐1, and interleukin‐1β (IL‐1β) and distribution of M1 macrophages were analysed by immunohistochemistry and immunofluorescence staining in vivo. Then, the mechanism of NLRP3 activation was further verified by macrophage and human periodontal ligament cell (hPDLC) co‐culture system in vitro. The production levels of NLRP3, caspase‐1, pro‐caspase‐1, and IL‐1β in M1 macrophages in the co‐culture system were detected by Western blot, and the polarization of CD68+IL‐1β+ M1 macrophages was detected by immunofluorescence staining. Results In the rat RR model, NLRP3, caspase‐1, IL‐1β, and M1 macrophages were expressed in periodontal ligament, mainly concentrated around RR areas. Force‐pre‐treated hPDLCs promoted M1 macrophage polarization and the production of NLRP3, caspase‐1, and IL‐1β in M1 macrophages in co‐culture system. When MCC950, an inhibitor of NLRP3 inflammasome, was added, NLRP3 activation and M1 macrophage polarization were inhibited. Conclusions In periodontal tissues, hPDLCs stimulated by force promoted M1 macrophage polarization and increased IL‐1β production by activating NLRP3 inflammasome in M1 macrophages, thus initiating the occurrence of RR.

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Natural Compounds as Regulators of NLRP3 Inflammasome-Mediated IL-1βProduction

Cited by 110 publications

References 128 publications

Natural Biflavonoids Modulate Macrophage–Oxidized LDL Interaction In Vitro and Promote Atheroprotection In Vivo

Natural Biflavonoids Modulate Macrophage–Oxidized LDL Interaction In Vitro and Promote Atheroprotection In Vivo

<p>In vitro expression of NLRP inflammasome-induced active Caspase-1 expression in normal human epidermal keratinocytes (NHEK) by various exogenous threats and subsequent inhibition by naturally derived ingredient blends</p>

NLRP3 inflammasome mediates M1 macrophage polarization and IL‐1β production in inflammatory root resorption

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