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  1. Article ; Online: Multiomic Signatures of Chronic Beryllium Disease Bronchoalveolar Lavage Cells Relate to T-Cell Function and Innate Immunity.

    Li, Li / Konigsberg, Iain R / Bhargava, Maneesh / Liu, Sucai / MacPhail, Kristyn / Mayer, Annyce / Davidson, Elizabeth J / Liao, Shu-Yi / Lei, Zhe / Mroz, Peggy M / Fingerlin, Tasha E / Yang, Ivana V / Maier, Lisa A

    American journal of respiratory cell and molecular biology

    2022  Volume 67, Issue 6, Page(s) 632–640

    Abstract: Chronic beryllium disease (CBD) is a Th1 granulomatous lung disease preceded by sensitization to beryllium (BeS). We profiled the methylome, transcriptome, and selected proteins in the lung to identify molecular signatures and networks associated with ... ...

    Abstract Chronic beryllium disease (CBD) is a Th1 granulomatous lung disease preceded by sensitization to beryllium (BeS). We profiled the methylome, transcriptome, and selected proteins in the lung to identify molecular signatures and networks associated with BeS and CBD. BAL cell DNA and RNA were profiled using microarrays from CBD (
    MeSH term(s) Humans ; Berylliosis/genetics ; T-Lymphocytes ; Bronchoalveolar Lavage ; Bronchoalveolar Lavage Fluid ; Immunity, Innate/genetics ; RNA ; Chronic Disease
    Chemical Substances BES (10191-18-1) ; RNA (63231-63-0)
    Language English
    Publishing date 2022-08-16
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 1025960-0
    ISSN 1535-4989 ; 1044-1549
    ISSN (online) 1535-4989
    ISSN 1044-1549
    DOI 10.1165/rcmb.2022-0077OC
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Beryllium-induced lung disease exhibits expression profiles similar to sarcoidosis.

    Li, Li / Silveira, Lori J / Hamzeh, Nabeel / Gillespie, May / Mroz, Peggy M / Mayer, Annyce S / Fingerlin, Tasha E / Maier, Lisa A

    The European respiratory journal

    2016  Volume 47, Issue 6, Page(s) 1797–1808

    Abstract: A subset of beryllium-exposed workers develop beryllium sensitisation (BeS) which precedes chronic beryllium disease (CBD). We conducted an in-depth analysis of differentially expressed candidate genes in CBD.We performed Affymetrix GeneChip 1.0 ST array ...

    Abstract A subset of beryllium-exposed workers develop beryllium sensitisation (BeS) which precedes chronic beryllium disease (CBD). We conducted an in-depth analysis of differentially expressed candidate genes in CBD.We performed Affymetrix GeneChip 1.0 ST array analysis on peripheral blood mononuclear cells (PBMCs) from 10 CBD, 10 BeS and 10 beryllium-exposed, nondiseased controls stimulated with BeSO4 or medium. The differentially expressed genes were validated by high-throughput real-time PCR in this group and in an additional group of cases and nonexposed controls. The functional roles of the top candidate genes in CBD were assessed using a pharmacological inhibitor. CBD gene expression data were compared with whole blood and lung tissue in sarcoidosis from the Gene Expression Omnibus.We confirmed almost 450 genes that were significantly differentially expressed between CBD and controls. The top enrichment of genes was for JAK (Janus kinase)-STAT (signal transducer and activator of transcription) signalling. A JAK2 inhibitor significantly decreased tumour necrosis factor-α and interferon-γ production. Furthermore, we found 287 differentially expressed genes overlapped in CBD/sarcoidosis. The top shared pathways included cytokine-cytokine receptor interactions, and Toll-like receptor, chemokine and JAK-STAT signalling pathways.We show that PBMCs demonstrate differentially expressed gene profiles relevant to the immunnopathogenesis of CBD. CBD and sarcoidosis share similar differential expression of pathogenic genes and pathways.
    Language English
    Publishing date 2016-06
    Publishing country England
    Document type Journal Article
    ZDB-ID 639359-7
    ISSN 1399-3003 ; 0903-1936
    ISSN (online) 1399-3003
    ISSN 0903-1936
    DOI 10.1183/13993003.01469-2015
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: DNA Methylation Changes in Lung Immune Cells Are Associated with Granulomatous Lung Disease.

    Yang, Ivana V / Konigsberg, Iain / MacPhail, Kristyn / Li, Li / Davidson, Elizabeth J / Mroz, Peggy M / Hamzeh, Nabeel / Gillespie, May / Silveira, Lori J / Fingerlin, Tasha E / Maier, Lisa A

    American journal of respiratory cell and molecular biology

    2018  Volume 60, Issue 1, Page(s) 96–105

    Abstract: Epigenetic marks are likely to explain variability of response to antigen in granulomatous lung disease. The objective of this study was to identify DNA methylation and gene expression changes associated with chronic beryllium disease (CBD) and ... ...

    Abstract Epigenetic marks are likely to explain variability of response to antigen in granulomatous lung disease. The objective of this study was to identify DNA methylation and gene expression changes associated with chronic beryllium disease (CBD) and sarcoidosis in lung cells obtained by BAL. BAL cells from CBD (n = 8), beryllium-sensitized (n = 8), sarcoidosis (n = 8), and additional progressive sarcoidosis (n = 9) and remitting (n = 15) sarcoidosis were profiled on the Illumina 450k methylation and Affymetrix/Agilent gene expression microarrays. Statistical analyses were performed to identify DNA methylation and gene expression changes associated with CBD, sarcoidosis, and disease progression in sarcoidosis. DNA methylation array findings were validated by pyrosequencing. We identified 52,860 significant (P < 0.005 and q < 0.05) CpGs associated with CBD; 2,726 CpGs near 1,944 unique genes have greater than 25% methylation change. A total of 69% of differentially methylated genes are significantly (q < 0.05) differentially expressed in CBD, with many canonical inverse relationships of methylation and expression in genes critical to T-helper cell type 1 differentiation, chemokines and their receptors, and other genes involved in immunity. Testing of these CBD-associated CpGs in sarcoidosis reveals that methylation changes only approach significance, but are methylated in the same direction, suggesting similarities between the two diseases with more heterogeneity in sarcoidosis that limits power with the current sample size. Analysis of progressive versus remitting sarcoidosis identified 15,215 CpGs (P < 0.005 and q < 0.05), but only 801 of them have greater than 5% methylation change, demonstrating that DNA methylation marks of disease progression changes are more subtle. Our study highlights the significance of epigenetic marks in lung immune response in granulomatous lung disease.
    MeSH term(s) Berylliosis/genetics ; Berylliosis/immunology ; Berylliosis/pathology ; Biomarkers/analysis ; Case-Control Studies ; Chronic Disease ; DNA Methylation ; Female ; Gene Expression Profiling ; Gene Expression Regulation ; Genome, Human ; Humans ; Male ; Middle Aged ; Sarcoidosis, Pulmonary/genetics ; Sarcoidosis, Pulmonary/immunology ; Sarcoidosis, Pulmonary/pathology
    Chemical Substances Biomarkers
    Language English
    Publishing date 2018-09-04
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 1025960-0
    ISSN 1535-4989 ; 1044-1549
    ISSN (online) 1535-4989
    ISSN 1044-1549
    DOI 10.1165/rcmb.2018-0177OC
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Beryllium increases the CD14(dim)CD16+ subset in the lung of chronic beryllium disease.

    Li, Li / Hamzeh, Nabeel / Gillespie, May / Elliott, Jill / Wang, Jieru / Gottschall, Eva Brigitte / Mroz, Peggy M / Maier, Lisa A

    PloS one

    2015  Volume 10, Issue 2, Page(s) e0117276

    Abstract: CD14dimCD16+ and CD14brightCD16+ cells, which compose a minor population of monocytes in human peripheral blood mononuclear cells (PBMC), have been implicated in several inflammatory diseases. The aim of this study was to investigate whether this ... ...

    Abstract CD14dimCD16+ and CD14brightCD16+ cells, which compose a minor population of monocytes in human peripheral blood mononuclear cells (PBMC), have been implicated in several inflammatory diseases. The aim of this study was to investigate whether this phenotype was present as a subset of lung infiltrative alveolar macrophages (AMs) in the granulomatous lung disease, chronic beryllium disease (CBD). The monocytes subsets was determined from PBMC cells and bronchoalveolar lavage (BAL) cells from CBD, beryllium sensitized Non-smoker (BeS-NS) and healthy subjects (HS) using flow cytometry. The impact of smoking on the AMs cell phenotype was determined by using BAL cells from BeS smokers (BeS-S). In comparison with the other monocyte subpopulations, CD14dimCD16+ cells were at decreased frequency in PBMCs of both BeS-NS and CBD and showed higher HLA-DR expression, compared to HS. The AMs from CBD and BeS-NS demonstrated a CD14dimCD16+phenotype, while CD14brightCD16+ cells were found at increased frequency in AMs of BeS, compared to HS. Fresh AMs from BeS-NS and CBD demonstrated significantly greater CD16, CD40, CD86 and HLA-DR than HS and BeS-S. The expression of CD16 on AMs from both CBD and BeS-NS was downregulated significantly after 10μM BeSO4 stimulation. The phagocytic activity of AMs decreased after 10μM BeSO4 treatment in both BeS-NS and CBD, although was altered or reduced in HS and BeS-S. These results suggest that Be increases the CD14dimCD16+ subsets in the lung of CBD subjects. We speculate that Be-stimulates the compartmentalization of a more mature CD16+ macrophage phenotype and that in turn these macrophages are a source of Th1 cytokines and chemokines that perpetuate the Be immune response in CBD. The protective effect of cigarette smoking in BeS-S may be due to the low expression of co-stimulatory markers on AMs from smokers as well as the decreased phagocytic function.
    MeSH term(s) Aged ; Berylliosis/metabolism ; Berylliosis/pathology ; Beryllium/pharmacology ; Bronchoalveolar Lavage Fluid/cytology ; Chemokines/metabolism ; Chronic Disease ; Cytokines/metabolism ; Female ; HLA-DR Antigens/metabolism ; Humans ; Leukocytes, Mononuclear/cytology ; Leukocytes, Mononuclear/drug effects ; Leukocytes, Mononuclear/metabolism ; Lipopolysaccharide Receptors/metabolism ; Lung/cytology ; Lung/metabolism ; Lung/pathology ; Macrophages, Alveolar/cytology ; Macrophages, Alveolar/drug effects ; Macrophages, Alveolar/metabolism ; Male ; Middle Aged ; Monocytes/cytology ; Monocytes/immunology ; Phagocytosis/drug effects ; Phenotype ; Receptors, IgG/metabolism
    Chemical Substances Chemokines ; Cytokines ; HLA-DR Antigens ; Lipopolysaccharide Receptors ; Receptors, IgG ; beryllium sulfate (01UQ1KPC7E) ; Beryllium (OW5102UV6N)
    Language English
    Publishing date 2015-02-17
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ISSN 1932-6203
    ISSN (online) 1932-6203
    DOI 10.1371/journal.pone.0117276
    Database MEDical Literature Analysis and Retrieval System OnLINE

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