Microarray-Based Analysis of the Lung Recovery Process After Stainless-Steel Welding Fume Exposure in Sprague–Dawley Rats

Oh, Jung‐Hwa; Yang, Mi-Jin; Yang, Young-Su; Park, Han-Jin; Heo, Sun Hee; Lee, Eun-Hee; Song, Chang-Woo; Yoon, Seokjoo

doi:10.1080/08958370802464281

Cited by 17 publications

(14 citation statements)

References 35 publications

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“…Expression levels of this proteolytic gene are primarily associated with macrophages; therefore, its overexpression may reflect an ongoing macrophage accumulation and/or activation in the A/J lung. Further, MMP12 was recently shown to play a key role in welding fume-induced lung inflammation as well as in fibrotic diseases such as asbestosis [12,26,27]. Nine genes in the other top network, drug metabolism, lipid metabolism and small molecule biochemistry were upregulated including cytochrome P450, family 1, subfamily B, polypeptide 1 ( CYP1B1 ), ubiquitin D ( UBD ), cholesterol 25-hydroxylase ( CH25H ), delta-like 1 homolog [Drosophila] ( DLK1 ), and interleukin 4 induced 1 ( IL41 ) (Figure 7, panel B).…”

Section: Resultsmentioning

confidence: 99%

Response of the mouse lung transcriptome to welding fume: effects of stainless and mild steel fumes on lung gene expression in A/J and C57BL/6J mice

Zeidler-Erdely

Kashon

et al. 2010

Respir Res

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BackgroundDebate exists as to whether welding fume is carcinogenic, but epidemiological evidence suggests that welders are an at risk population for the development of lung cancer. Recently, we found that exposure to welding fume caused an acutely greater and prolonged lung inflammatory response in lung tumor susceptible A/J versus resistant C57BL/6J (B6) mice and a trend for increased tumor incidence after stainless steel (SS) fume exposure. Here, our objective was to examine potential strain-dependent differences in the regulation and resolution of the lung inflammatory response induced by carcinogenic (Cr and Ni abundant) or non-carcinogenic (iron abundant) metal-containing welding fumes at the transcriptome level.MethodsMice were exposed four times by pharyngeal aspiration to 5 mg/kg iron abundant gas metal arc-mild steel (GMA-MS), Cr and Ni abundant GMA-SS fume or vehicle and were euthanized 4 and 16 weeks after the last exposure. Whole lung microarray using Illumina Mouse Ref-8 expression beadchips was done.ResultsOverall, we found that tumor susceptibility was associated with a more marked transcriptional response to both GMA-MS and -SS welding fumes. Also, Ingenuity Pathway Analysis revealed that gene regulation and expression in the top molecular networks differed between the strains at both time points post-exposure. Interestingly, a common finding between the strains was that GMA-MS fume exposure altered behavioral gene networks. In contrast, GMA-SS fume exposure chronically upregulated chemotactic and immunomodulatory genes such as CCL3, CCL4, CXCL2, and MMP12 in the A/J strain. In the GMA-SS-exposed B6 mouse, genes that initially downregulated cellular movement, hematological system development/function and immune response were involved at both time points post-exposure. However, at 16 weeks, a transcriptional switch to an upregulation for neutrophil chemotactic genes was found and included genes such as S100A8, S100A9 and MMP9.ConclusionsCollectively, our results demonstrate that lung tumor susceptibility may predispose the A/J strain to a prolonged dysregulation of immunomodulatory genes, thereby delaying the recovery from welding fume-induced lung inflammation. Additionally, our results provide unique insight into strain- and welding fume-dependent genetic factors involved in the lung response to welding fume.

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Section: Resultsmentioning

confidence: 99%

Response of the mouse lung transcriptome to welding fume: effects of stainless and mild steel fumes on lung gene expression in A/J and C57BL/6J mice

Zeidler-Erdely

Kashon

et al. 2010

Respir Res

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“…from blood. Earlier studies have shown a large difference in gene expression in lungs compared to blood in rats after exposure to welding fumes (Oh et al 2009;Rim et al 2004). Furthermore, we used a self-control design of the study, meaning that a person was its own control, which reduces problems with matching of symptomatic and nonsymptomatic groups.…”

Section: Discussionmentioning

confidence: 97%

Gene expression analysis in induced sputum from welders with and without airway-related symptoms

Jönsson

Nielsen

Broberg

2010

Int Arch Occup Environ Health

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Workers' exposure to welding fumes changed gene expression in the lower airways in genes involved in inflammatory and defence response. Thus, microarray and qPCR technique can demonstrate markers of exposure to welding fumes and possible disease-related markers. However, further studies are needed to verify genes involved and to further characterise the mechanism for welding fumes-associated lower airway symptoms.

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“…Results of lung gene expression studies in both mice and rats indicate a strong immunologic transcriptional response to welding fume (Oh et al, 2009(Oh et al, , 2011Yang et al, 2009;Zeidler-Erdely et al, 2010). A 30-day inhalation exposure to MMA-SS fume in rats resulted in marked changes in several immune-related genes, including matrix metalloproteinase-12 (Mmp12), Cd 5 moleculelike (Cd5l), chemokine (C-C motif) ligand 7 (Ccl7), C-X-C motif chemokine 5 (Cxcl5), and secreted phosphoprotein 1 (Spp1).…”

Section: Animal Immunotoxicity Studiesmentioning

confidence: 99%

Immunotoxicology of arc welding fume: Worker and experimental animal studies

Zeidler-Erdely

Erdely

Antonini

2012

Journal of Immunotoxicology

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Microarray-Based Analysis of the Lung Recovery Process After Stainless-Steel Welding Fume Exposure in Sprague–Dawley Rats

Cited by 17 publications

References 35 publications

Response of the mouse lung transcriptome to welding fume: effects of stainless and mild steel fumes on lung gene expression in A/J and C57BL/6J mice

Response of the mouse lung transcriptome to welding fume: effects of stainless and mild steel fumes on lung gene expression in A/J and C57BL/6J mice

Gene expression analysis in induced sputum from welders with and without airway-related symptoms

Immunotoxicology of arc welding fume: Worker and experimental animal studies

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