Dataset Information

Transcriptional Response of Blood Mononuclear Cells from Patients with Inflammatory and Autoimmune Disorders Exposed to "Krakow Smog".

ABSTRACT: Despite the general awareness of the need to reduce air pollution, the efforts were undertaken in Poland to eliminate the pollutants and their harmful effect on human health seem to be insufficient. Moreover, the latest data indicate that the city of Krakow is at the forefront of the most polluted cities worldwide. Hence, in this report, we investigated the impact of particulate matter isolated from the air of Krakow (PM KRK) on the gene expression profile of peripheral blood mononuclear cells (PBMCs) in healthy donors (HD) and patients with atherosclerosis (AS), rheumatoid arthritis (RA) and multiple sclerosis (MS), after in vitro exposure. Blood samples were collected in two seasons, differing in the concentration of PM in the air (below or above a daily limit of 50 µg/m³ for PM 10). Data show that PBMCs exposed in vitro to PM KRK upregulated the expression of genes involved, among others, in pro-inflammatory response, cell motility, and regulation of cell metabolism. The transcriptional effects were observed predominantly in the group of patients with AS and MS. The observed changes seem to be dependent on the seasonal concentration of PM in the air of Krakow and may suggest their important role in the progression of AS, MS, and RA in the residents of Krakow.

SUBMITTER: Galuszka-Bulaga A

PROVIDER: S-EPMC9406644 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature

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Transcriptional Response of Blood Mononuclear Cells from Patients with Inflammatory and Autoimmune Disorders Exposed to "Krakow Smog".

Gałuszka-Bulaga Adrianna A Hajto Jacek J Borczyk Małgorzata M Gołda Sławomir S Piechota Marcin M Korostyński Michał M Rutkowska-Zapała Magdalena M Latacz Paweł P Guła Zofia Z Korkosz Mariusz M Pera Joanna J Słowik Agnieszka A Siedlar Maciej M Baran Jarek J

Cells 20220819 16

Despite the general awareness of the need to reduce air pollution, the efforts were undertaken in Poland to eliminate the pollutants and their harmful effect on human health seem to be insufficient. Moreover, the latest data indicate that the city of Krakow is at the forefront of the most polluted cities worldwide. Hence, in this report, we investigated the impact of particulate matter isolated from the air of Krakow (PM KRK) on the gene expression profile of peripheral blood mononuclear cells ( ...[more]

PMID: 36010662

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Project description:IntroductionAtaxia telangiectasia (A-T) is an autosomal recessive neurodegenerative disease with widespread systemic manifestations and marked variability in clinical phenotypes. In this study, we sought to determine whether transcriptomic profiling of peripheral blood mononuclear cells (PBMCs) defines subsets of individuals with A-T beyond mild and classic phenotypes, enabling identification of novel features for disease classification and treatment response to therapy.MethodsParticipants with classic A-T (n = 77), mild A-T (n = 13), and unaffected controls (n = 15) were recruited from two outpatient clinics. PBMCs were isolated and bulk RNAseq was performed. Plasma was also isolated in a subset of individuals. Affected individuals were designated mild or classic based on ATM mutations and clinical and laboratory features.ResultsPeople with classic A-T were more likely to be younger and IgA deficient and to have higher alpha-fetoprotein levels and lower % forced vital capacity compared to individuals with mild A-T. In classic A-T, the expression of genes required for V(D)J recombination was lower, and the expression of genes required for inflammatory activity was higher. We assigned inflammatory scores to study participants and found that inflammatory scores were highly variable among people with classic A-T and that higher scores were associated with lower ATM mRNA levels. Using a cell type deconvolution approach, we inferred that CD4 + T cells and CD8 + T cells were lower in number in people with classic A-T. Finally, we showed that individuals with classic A-T exhibit higher SERPINE1 (PAI-1) mRNA and plasma protein levels, irrespective of age, and higher FLT4 (VEGFR3) and IL6ST (GP130) plasma protein levels compared with mild A-T and controls.ConclusionUsing a transcriptomic approach, we identified novel features and developed an inflammatory score to identify subsets of individuals with different inflammatory phenotypes in A-T. Findings from this study could be used to help direct treatment and to track treatment response to therapy.

Project description:Inflammatory reactions associated with osteolysis and aseptic loosening are the result of wear particles generated at the articulating surfaces of implant components. The aim of the present study was to analyze the biological response of human osteoblasts and peripheral blood mononuclear cells (PBMCs) after exposure to metallic and alumina ceramic particles regarding cellular differentiation, cytokine release, and monocyte migration. Cells were exposed to particles (0.01 and 0.05 mg/ml) from an alumina matrix composite (AMC) ceramic and a CoCr28Mo6 alloy with an average size of 0.5 µm over 48 and 96 h. The expression rates of osteogenic (Col1A1, ALP) and pro-osteoclastic (RANK, Trap5b) differentiation markers as well as pro-osteolytic mediators (MMP-1, TIMP-1, IL-6, IL-8, MCP-1) were determined and soluble protein concentrations of active MMP-1, IL-6, IL-8, and pro-collagen type 1 in cell culture supernatants were evaluated. Additionally, the capacity of particle-treated osteoblasts to attract potentially pro-inflammatory cells to the site of particle exposure was investigated by migration assays using osteoblast-conditioned media. The cellular morphology and metabolism of human osteoblasts and adherent PBMCs were influenced by particle type and concentration. In human osteoblasts, Col1A1 expression rates and protein production were significantly reduced after exposing cells to the lower concentration of cobalt-chromium (CoCr) and AMC particles. Exposure to AMC particles (0.01 mg/ml) resulted in increased mRNA levels of RANK and Trap5b in adherent PBMCs. For MMP-1 gene expression, elevated levels were more prominent after incubation with CoCr compared to AMC particles in osteoblasts, which was not reflected by the protein data. Interleukin (IL)-6 and IL-8 mRNA and protein were induced in both cell types after treatment with AMC particles, whereas exposure to CoCr particles resulted in significantly upregulated IL-6 and IL-8 protein contents in PBMCs only. Exposure of osteoblasts to CoCr particles reduced the chemoattractant potential of osteoblast-conditioned medium. Our results demonstrate distinct effects of AMC and CoCr particles in human osteoblasts and PBMCs. Complex cell and animal models are required to further evaluate the impact of cellular interactions between different cell types during particle exposure.

Dataset Information

Transcriptional Response of Blood Mononuclear Cells from Patients with Inflammatory and Autoimmune Disorders Exposed to "Krakow Smog".

Publications

Transcriptional Response of Blood Mononuclear Cells from Patients with Inflammatory and Autoimmune Disorders Exposed to "Krakow Smog".

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