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Actin polymerization plays a significant role in asbestos-induced inflammasome activation in mesothelial cells in vitro.
- Source :
-
Histochemistry and cell biology [Histochem Cell Biol] 2017 May; Vol. 147 (5), pp. 595-604. Date of Electronic Publication: 2016 Dec 24. - Publication Year :
- 2017
-
Abstract
- Asbestos exposure leads to malignant mesothelioma (MM), a deadly neoplasm of mesothelial cells of various locations. Although there is no doubt about the role of asbestos in MM tumorigenesis, mechanisms are still not well explored. Recently, our group demonstrated that asbestos causes inflammasome priming and activation in mesothelial cells, which in part is dependent on oxidative stress. Our current study sheds light on yet another mechanism of inflammasome activation by asbestos. Here we show the role of actin polymerization in asbestos-induced activation of the nod-like receptor pyrin domain-containing protein 3 (NLRP3) inflammasome. Using human mesothelial cells, we first demonstrate that asbestos and carbon nanotubes induced caspase-1 activation and high-mobility group box 1, interleukin 1 beta and interleukin 18 secretion was blocked by Cytochalasin D (Cyto D) an actin polymerization inhibitor. Next, to understand the mechanism, we assessed whether phagocytosis of fibers by mesothelial cells is affected by actin polymerization inhibition. Transmission electron microscopy showed the inhibition of fiber uptake by mesothelial cells in the presence of Cyto D. Furthermore, localization of components of the inflammasome, apoptotic speck-like protein containing a CARD domain (ASC) and NLRP3, to the perinuclear space in mitochondria or endoplasmic reticulum in response to fiber exposure was also interrupted in the presence of Cyto D. Taken together, our studies suggest that actin polymerization plays important roles in inflammasome activation by fibers via regulation of phagocytosis and/or spatial localization of inflammasome components.
- Subjects :
- Actins antagonists & inhibitors
Asbestos antagonists & inhibitors
Cell Survival drug effects
Cells, Cultured
Cytochalasin D pharmacology
Dose-Response Relationship, Drug
Epithelial Cells metabolism
Humans
Inflammasomes metabolism
Polymerization drug effects
Structure-Activity Relationship
Actins metabolism
Asbestos adverse effects
Epithelial Cells drug effects
Inflammasomes drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1432-119X
- Volume :
- 147
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Histochemistry and cell biology
- Publication Type :
- Academic Journal
- Accession number :
- 28013367
- Full Text :
- https://doi.org/10.1007/s00418-016-1530-8