Dataset Information

Modulation of macrophage activities in proliferation, lysosome, and phagosome by the nonspecific immunostimulator, mica.

ABSTRACT: It was reported that the aluminosilicate material mica activated macrophages and showed its immunostimulating effects. However, the mechanisms by which it exerts these effects are unclear. To address this, we evaluated the effects of mica fine particles (MFP, 804.1 ± 0.02 nm) on the murine macrophage cell line, RAW 264.7. Specifically, RAW 264.7 cells were treated with 100 and 500 ?g/mL MFP and their proliferative response was determined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Changes in global gene expression upon MFP treatment for 12 and 48 h were also determined using microarrays. Following the MFP treatment, RAW 264.7 cells showed a low level of proliferation compared to nontreated cells (p < 0.01). There was a change in an expression level of 1,128 genes after 48 h treatment. Specifically, genes associated with the cell cycle, DNA replication, and pyrimidine and purine metabolisms, were down-regulated in cells treated with MFP, which resulted in reduction of cell proliferation. MFP treatment also up-regulated genes associated with lysosome and phagosome function, which are both required for macrophage activities. We speculate that activation of macrophages by mica is in part derived from up-regulation of these pathways.

SUBMITTER: Jung M

PROVIDER: S-EPMC4323240 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Modulation of macrophage activities in proliferation, lysosome, and phagosome by the nonspecific immunostimulator, mica.

Jung Myunghwan M Shin Min-Kyoung MK Jung Yeon-Kwon YK Yoo Han Sang HS

PloS one 20150210 2

It was reported that the aluminosilicate material mica activated macrophages and showed its immunostimulating effects. However, the mechanisms by which it exerts these effects are unclear. To address this, we evaluated the effects of mica fine particles (MFP, 804.1 ± 0.02 nm) on the murine macrophage cell line, RAW 264.7. Specifically, RAW 264.7 cells were treated with 100 and 500 μg/mL MFP and their proliferative response was determined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazo ...[more]

PMID: 25668030

Similar Datasets

Project description:Francisella tularensis is a highly infectious facultative intracellular bacterium that can be transmitted between mammals by arthropod vectors. Similar to many other intracellular bacteria that replicate within the cytosol, such as Listeria, Shigella, Burkholderia, and Rickettsia, the virulence of F. tularensis depends on its ability to modulate biogenesis of its phagosome and to escape into the host cell cytosol where it proliferates. Recent studies have identified the F. tularensis genes required for modulation of phagosome biogenesis and escape into the host cell cytosol within human and arthropod-derived cells. However, the arthropod and mammalian host factors required for intracellular proliferation of F. tularensis are not known. We have utilized a forward genetic approach employing genome-wide RNAi screen in Drosophila melanogaster-derived cells. Screening a library of approximately 21,300 RNAi, we have identified at least 186 host factors required for intracellular bacterial proliferation. We silenced twelve mammalian homologues by RNAi in HEK293T cells and identified three conserved factors, the PI4 kinase PI4KCA, the ubiquitin hydrolase USP22, and the ubiquitin ligase CDC27, which are also required for replication in human cells. The PI4KCA and USP22 mammalian factors are not required for modulation of phagosome biogenesis or phagosomal escape but are required for proliferation within the cytosol. In contrast, the CDC27 ubiquitin ligase is required for evading lysosomal fusion and for phagosomal escape into the cytosol. Although F. tularensis interacts with the autophagy pathway during late stages of proliferation in mouse macrophages, this does not occur in human cells. Our data suggest that F. tularensis utilizes host ubiquitin turnover in distinct mechanisms during the phagosomal and cytosolic phases and phosphoinositide metabolism is essential for cytosolic proliferation of F. tularensis. Our data will facilitate deciphering molecular ecology, patho-adaptation of F. tularensis to the arthropod vector and its role in bacterial ecology and patho-evolution to infect mammals.

Dataset Information

Modulation of macrophage activities in proliferation, lysosome, and phagosome by the nonspecific immunostimulator, mica.

Publications

Modulation of macrophage activities in proliferation, lysosome, and phagosome by the nonspecific immunostimulator, mica.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets