Actin polymerization plays a significant role in asbestos-induced inflammasome activation in mesothelial cells in vitro

MacPherson, Maximilian B.; Westbom, Catherine M.; Kogan, Helen; Shukla, Arti

doi:10.1007/s00418-016-1530-8

Cited by 9 publications

(8 citation statements)

References 15 publications

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“…f‐Actin was evident in the inflammasome complexes in primary human microglia (Figure 5f,g). This is not unprecedented; the presence of f‐actin associated with NLRP3 inflammasomes has been reported by others for mouse macrophages activated by ATP, nigericin, or asbestos (Burger, Fickentscher, de Moerloose, & Brandt, 2016; MacPherson, Westbom, Kogan, & Shukla, 2017).…”

Section: Resultsmentioning

confidence: 74%

α‐Synuclein evokes NLRP3 inflammasome‐mediated IL‐1β secretion from primary human microglia

Pike

Varanita

Herrebout

et al. 2021

Glia

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Synucleinopathies such as Parkinson's disease (PD) are hallmarked by α‐synuclein (α‐syn) pathology and neuroinflammation. This neuroinflammation involves activated microglia with increased secretion of interleukin‐1β (IL‐1β). The main driver of IL‐1β secretion from microglia is the NLRP3 inflammasome. A critical link between microglial NLRP3 inflammasome activation and the progression of both α‐syn pathology and dopaminergic neurodegeneration has been identified in various PD models in vivo. α‐Syn is known to activate the microglial NLRP3 inflammasome in murine models, but its relationship to this inflammasome in human microglia has not been established. In this study, IL‐1β secretion from primary mouse microglia induced by α‐syn fibrils was dependent on NLRP3 inflammasome assembly and caspase‐1 activity, as previously reported. We show that exposure of primary human microglia to α‐syn fibrils also resulted in significant IL‐1β secretion that was dependent on inflammasome assembly and involved the recruitment of caspase‐1 protein to inflammasome scaffolds as visualized with superresolution microscopy. While canonical IL‐1β secretion was clearly dependent on caspase‐1 enzymatic activity, this activity was less clearly involved for α‐syn‐induced IL‐1β secretion from human microglia. This work presents similarities between primary human and mouse microglia in the mechanisms of activation of the NLRP3 inflammasome by α‐syn, but also highlights evidence to suggest that there may be a difference in the requirement for caspase‐1 activity in IL‐1β output. The data represent a novel characterization of PD‐related NLRP3 inflammasome activation in primary human microglia and further implicate this mechanism in the pathology underlying PD.

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Section: Resultsmentioning

confidence: 74%

α‐Synuclein evokes NLRP3 inflammasome‐mediated IL‐1β secretion from primary human microglia

Pike

Varanita

Herrebout

et al. 2021

Glia

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Section: Cytoskeleton‐mediated Inflammasome Regulationmentioning

confidence: 86%

“…Some inconsistencies in the data thus far reported on the cytoskeleton and mechanoregulation of inflammasome activation reveal the complex regulatory mechanisms involved. For instance, cytochalasin D induced actin depolymerization has also been reported to reduce inflammasome activation and cyclic stretch reduced IL‐1β secretion via adenosine monophosphate kinase (AMPK) mediated caspase‐1 inhibition . Although the differences may be due to differences in cell type and inflammasome activator, much work remains to be done to clarify how F‐actin and other cytoskeletal components modify inflammatory outcomes …”

Section: Discussionmentioning

confidence: 99%

“…In contrast, F‐actin depolymerization via cytochalasin D did attenuate asbestos‐induced NLRP3 activation and decreased maturation of IL‐1β and IL‐18 in mesothelial cells . F‐actin de‐polymerization limits phagocytosis of asbestos and the subcellular localization of inflammasome assembly . Actin polymerization is also required for NLRC4 activation in macrophages, as shown by reduced ASC speck formation and IL‐1β maturation following cytochalasin D treatment .…”

Section: Cytoskeleton‐mediated Inflammasome Regulationmentioning

confidence: 94%

“…Resistance to lung fibrosis corresponds with a reduction in IL‐1β‐mediated inflammation in the lungs . Intermediate filaments are essential to subcellular trafficking and the formation of mechanosensitive adhesive structures, such as podosomes . Thus, loss of vimentin can impair cellular adhesiveness and mechanosensitivity.…”

Section: Cytoskeleton‐mediated Inflammasome Regulationmentioning

confidence: 99%

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Cells under stress: The mechanical environment shapes inflammasome responses to danger signals

Joshi

Morley

2019

Journal of Leukocyte Biology

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Many intracellular signals, such as host danger-associated molecules and bacterial toxins during infection, elicit inflammasome activation. However, the mechanical environment in tissues may also influence the sensitivity of various inflammasomes to activation. The cellular mechanical environment is determined by the extracellular tissue stiffness, or its inverse, tissue compliance. Tissue stiffness is sensed by the intracellular cytoskeleton through a process termed mechanotransduction. Thus, extracellular compliance and the intracellular cytoskeleton may regulate the sensitivity of inflammasome activation. Control of proinflammatory signaling by tissue compliance may contribute to the pathogenesis of diseases such as ventilator-induced lung injury during bacterial pneumonia and tissue fibrosis in inflammatory disorders. The responsible signaling cascades in inflammasome activation pathways and mechanotransduction crosstalk are not yet fully understood. This rather different immunomodulatory perspective will be reviewed and open questions discussed here. K E Y W O R D S cell adhesion, inflammasome, inflammation, integrins, mechanobiology, monocytes/macrophages

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Exogenous nanoparticles and endogenous crystalline molecules as danger signals for the NLRP3 inflammasomes

Shirasuna

Karasawa

Takahashi

2018

Journal Cellular Physiology

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Inflammasome mechanisms are involved as some of the pathways of sterile inflammation. Inflammasomes are large multiprotein complexes in the cytosol and are a key system for the production of the pivotal inflammatory cytokines, interleukin (IL)-1β and IL-18, and inflammatory cell death called pyroptosis. Although a number of inflammasomes have been described, the nucleotide-binding oligomerization domain-, leucine-rich repeat-, and pyrin domain-containing 3 (NLRP3) is the most extensively investigated inflammasome. Exogenous pathogen-associated molecular patterns released during infection and endogenous crystalline danger/damage-associated molecular patterns (DAMPs) are well-known activators of NLRP3 inflammasomes. In addition, nanoparticle-associated molecular patterns (NAMPs), which are mediated by synthetic materials, including nanomaterials and nanoparticles, are proposed to be new danger signals of NLRP3 inflammasomes. Importantly, NAMP-and DAMPtriggered inflammation, a defining characteristic in inflammatory diseases, is termed as sterile inflammation because it occurs in the absence of foreign pathogens. This review focuses on the role of inflammasomes in exogenous NAMP-and endogenous crystalline DAMP-mediated sterile inflammation. Moreover, many regulatory mechanisms have been identified to attenuate NLRP3 inflammasomes. Therefore, we also summarize endogenous negative regulators of NLRP3 inflammasome activation, particularly induced by NAMPs or crystalline DAMPs.

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Actin polymerization plays a significant role in asbestos-induced inflammasome activation in mesothelial cells in vitro

Cited by 9 publications

References 15 publications

α‐Synuclein evokes NLRP3 inflammasome‐mediated IL‐1β secretion from primary human microglia

α‐Synuclein evokes NLRP3 inflammasome‐mediated IL‐1β secretion from primary human microglia

Cells under stress: The mechanical environment shapes inflammasome responses to danger signals

Exogenous nanoparticles and endogenous crystalline molecules as danger signals for the NLRP3 inflammasomes

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