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- W4313373341 abstract "Abstract Mast cells (MCs) participate in allergic diseases by producing pro-inflammatory mediators and regulatory cytokines. After high affinity IgE (FceRI) receptor activation, they release tryptase, b-hexosaminidase and other preformed pro-inflammatory substances by anaphylactic degranulation. Also, upon stimulation through Toll-like receptor 4 (TLR4), they release pro-inflammatory mediators (such as Tumor Necrosis Factor, TNF), by piecemeal degranulation, orchestrating protective reactions against pathogens. Reactions involved in anaphylactic degranulation require specific vesicular-associated membrane proteins (VAMPs) involved in the latest step of exocytosis. However, the particular roles of VAMP proteins on piecemeal secretion observed after TLR4 receptor activation are not known. Utilizing RBL-2H3 cells differentiated to a pro-inflammatory phenotype, we investigated the role of VAMP8 and VAMP3 on lipopolysaccharide (LPS)-induced mediator secretion in MCs. Confocal microscopy images showed that, in non-stimulated cells, TNF localizes in VAMP3 and VAMP8-positive vesicles. After TLR4 stimulation, we observed an increase in TNF and VAMP8 co-localization, without any change on TNF and VAMP3 co-localization. Remarkably, VAMP8 blockade with specific siRNA impaired TNF secretion after LPS-challenge, while VAMP3 siRNA-mediated down regulation did not. Our data indicate that, although TNF is maintained in VAMP3-containing vesicles, TLR4 triggering leads to the secretion of TNF in VAMP8-containing carriers. Our results contribute to the description of the molecular events involved in late steps of TNF secretion induced by innate immune stimuli in that important immune cell type." @default.
- W4313373341 created "2023-01-06" @default.
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- W4313373341 date "2020-05-01" @default.
- W4313373341 modified "2023-10-01" @default.
- W4313373341 title "VAMP8 mediates TLR4-dependent TNF secretion in RBL-2H3 pro-inflammatory cells" @default.
- W4313373341 doi "https://doi.org/10.4049/jimmunol.204.supp.226.18" @default.
- W4313373341 hasPublicationYear "2020" @default.
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