Genomic analysis of human lung fibroblasts exposed to vanadium pentoxide to identify candidate genes for occupational bronchitis

Ingram, Jennifer L.; Antao-Menezes, Aurita; Turpin, Elizabeth A.; Wallace, Duncan G.; Mangum, James B.; Pluta, Linda; Thomas, Russell S.; Bonner, James C.

doi:10.1186/1465-9921-8-34

Cited by 34 publications

(30 citation statements)

References 39 publications

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“…In the present study, we found that V 2 O 5 did not stimulate fibroblast proliferation in vitro, nor did it increase collagen synthesis or increase TGF-␤1, the key growth factor that stimulates collagen synthesis. These findings are consistent with recent work from our laboratory wherein we showed that collagen genes (COL1A2, COL1A1, COL3A1), along with TGF-␤2 and its associated signaling intermediates SMAD1 and SMURF1 were all down-regulated by V 2 O 5 in cultures of 16Lu human lung fibroblasts (17). However, V 2 O 5 increases TGF-␤1 and collagen in the lungs of mice and rats.…”

Section: Discussionsupporting

confidence: 83%

“…Exogenously added catalase does not likely enter the intracellular compartment. In a previous report on global gene analysis of human lung fibroblasts exposed to V 2 O 5 in vitro, we observed that CXCL10, an IFN-inducible STAT-1-dependent gene, was increased in a time-dependent manner (17). In the present study, we confirmed this observation using quantitative real-time RT-PCR and ELISA.…”

Section: Discussionsupporting

confidence: 80%

“…Our recent Affymetrix microarray analysis of V 2 O 5 -treated human lung fibroblasts revealed induction of a STAT-dependent chemokine, CXCL10 (17). Quantitative real-time RT-PCR confirmed that V 2 O 5 increased gene expression of CXCL10 occurred with a temporal expression pattern similar to that of STAT-1 phosphorylation (Fig.…”

Section: O 5 Induction Of Ifn-inducible Chemokine Cxcl10 Is Mediamentioning

confidence: 70%

“…org). For most experiments, HLF 16Lu were used due to our previous work with these cells in elucidating mechanisms of vanadium-induced cell signaling and gene expression (15)(16)(17). Selected experiments compared all three different human lung fibroblast isolates.…”

Section: Cellsmentioning

confidence: 99%

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STAT-1 Signaling in Human Lung Fibroblasts Is Induced by Vanadium Pentoxide through an IFN-β Autocrine Loop

Antao-Menezes

Turpin

Bost

et al. 2008

The Journal of Immunology

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The inhalation of vanadium pentoxide (V2O5) results in bronchitis and airway fibrosis. The lung fibrotic response to V2O5 partially resolves where fibroblasts first proliferate and deposit collagen, but then undergo growth arrest and apoptosis. STAT-1 mediates fibroblast growth arrest and apoptosis. We previously reported that STAT-1 is a protective factor and mice lacking STAT-1 are more susceptible to lung fibrosis. We also reported that V2O5-induced STAT-1 phosphorylation in lung fibroblasts requires H2O2 and de novo protein synthesis. In this study, we identified IFN-β as the protein that mediates STAT-1 activation by V2O5 in normal human lung fibroblasts and identified NADPH and xanthine oxidase systems as sources of H2O2 that drive IFN-β gene expression. STAT-1 phosphorylation was decreased with neutralizing Abs to IFN-β as well as an inhibitor of JAK. V2O5 also increased transcription of an IFN-inducible and STAT-1-dependent chemokine, CXCL10. Inhibition of H2O2-generating enzyme systems NADPH oxidase by apocynin and xanthine oxidase by allopurinol individually reduced STAT-1 phosphorylation. Apocynin and allopurinol also decreased V2O5-induced IFN-β mRNA levels and CXCL10 expression. IFN-α transcription was inhibited only by allopurinol. Taken together, these data indicate that fibroblasts play a role in the innate immune response to vanadium-induced oxidative stress by synthesizing IFN-β and activating STAT-1 to cause growth arrest and increase levels of CXCL10, a potent antifibrotic factor. This mechanism is postulated to counterbalance profibrogenic mechanisms that follow V2O5 injury.

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Section: Discussionsupporting

confidence: 83%

Section: Discussionsupporting

confidence: 80%

Section: O 5 Induction Of Ifn-inducible Chemokine Cxcl10 Is Mediamentioning

confidence: 70%

Section: Cellsmentioning

confidence: 99%

See 2 more Smart Citations

STAT-1 Signaling in Human Lung Fibroblasts Is Induced by Vanadium Pentoxide through an IFN-β Autocrine Loop

Antao-Menezes

Turpin

Bost

et al. 2008

The Journal of Immunology

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“…Short-term exposure to vanadium can stimulate activation of multiple transcription factors (Chen et al, 1999;Ding et al, 1999;Huang et al, 2000;Wang et al, 2003), whereas the long-term exposure to V 2 O 5 suppresses more than 1000 genes, including 298 genes related to regulation of transcription (Ingram et al, 2007), especially interferon regulatory factors. It has been postulated that low-affinity B-lymphocyte clone recruitment and selection for both long-lived plasma cells and memory B-lymphocyte pathways in the germinal center depends on the transcription factor IRF-4 (interferon regulatory factor-4; Benson et al, 2007).…”

Section: Discussionmentioning

confidence: 99%

Vanadium Pentoxide Inhalation Provokes Germinal Center Hyperplasia and Suppressed Humoral Immune Responses

Piñón-Zárate

Rodríguez-Lara

Rojas-Lemus

et al. 2008

Journal of Immunotoxicology

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Vanadium, an important air pollutant derived from fuel product combustion, aggravates respiratory diseases and impairs cardiovascular function. In contrast, its effects on immune response are conflicting. The aim of our work was to determine if spleens of vanadium-exposed CD1 mice showed histological lesions that might result in immune response malfunction. One hundred and twelve CD-1 male mice were placed in an acrylic box and inhaled 0.02 M vanadium pentoxide (V 2 O 5 ); actual concentration in chamber ≈1.4 mg V 2 O 5 /m 3 ) for 1 hr/d, twice a week, for 12 wk. Control mice inhaled only vehicle. Eight mice were sacrificed prior to the exposures. Eight control and eight V 2 O 5 -exposed mice were sacrificed 24 hr after the second exposure of each week until the 12-wk study was over. Another 8 mice that completed the 12-wk regimen were immunized with recombinant Hepatitis B surface antigen (HBsAg; three times over an 8-wk period) before sacrifice and analyses of their levels of anti-HBsAg antibody (HBSAb) using ELISA. In all studies, at sacrifice, blood samples were obtained by direct heart puncture and the spleen was removed, weighed and processed for H-E staining and quantitation of CD19 cells. The results indicated that the spleen weight of V 2 O 5 -exposed animals peaked at 9 wk (546 ± 45 vs. 274 ± 27 mg, p < 0.0001) and thereafter progressively decreased (321 ± 39 mg at 12 wk, p < 0.001; control spleen = 298 ± 35 mg). Spleens of V 2 O 5 -exposed animals showed an increased number of very large and non-clearly delimited germinal centers (that contained more lymphocytes and megakaryocytes) compared to those of control mice. In addition, their red pulp was poorly delimited and had an increase in CD19+ cells within hyperplasic germinal nodes. The mean HBsAb levels in immunized control mice were greater than that in the exposed hosts (i.e., OD = 0.39 ± 0.03 vs. 0.11 ± 0.05, p < 0.01). HBsAb avidity dropped to a

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Function and regulation of microRNA‐31 in development and disease

Stepicheva

Song

2016

Molecular Reproduction Devel

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SUMMARY MicroRNAs (miRNAs) are small noncoding RNAs that orchestrate numerous cellular processes both under normal physiological conditions as well as in diseases. This review summarizes the functional roles and transcriptional regulation of the highly evolutionarily conserved miRNA, microRNA-31 (miR-31). miR-31 is an important regulator of embryonic implantation, development, bone and muscle homeostasis, and immune system function. Its own regulation is disrupted during the onset and progression of cancer and autoimmune disorders such as psoriasis and systemic lupus erythematosus. Limited studies suggest that miR-31 is transcriptionally regulated by epigenetics, such as methylation and acetylation, as well as by a number of transcription factors. Overall, miR-31 regulates diverse cellular and developmental processes by targeting genes involved in cell proliferation, apoptosis, cell differentiation, and cell motility.

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Genomic analysis of human lung fibroblasts exposed to vanadium pentoxide to identify candidate genes for occupational bronchitis

Cited by 34 publications

References 39 publications

STAT-1 Signaling in Human Lung Fibroblasts Is Induced by Vanadium Pentoxide through an IFN-β Autocrine Loop

STAT-1 Signaling in Human Lung Fibroblasts Is Induced by Vanadium Pentoxide through an IFN-β Autocrine Loop

Vanadium Pentoxide Inhalation Provokes Germinal Center Hyperplasia and Suppressed Humoral Immune Responses

Function and regulation of microRNA‐31 in development and disease

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