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
<p>Abstract</p> <p>Background</p> <p>Debate 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 acu...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
| Published: |
BMC
2010-06-01
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| Series: | Respiratory Research |
| Online Access: | http://respiratory-research.com/content/11/1/70 |
| _version_ | 1818083568535994368 |
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| author | Antonini James M Li Shengqiao Kashon Michael L Zeidler-Erdely Patti C |
| author_facet | Antonini James M Li Shengqiao Kashon Michael L Zeidler-Erdely Patti C |
| author_sort | Antonini James M |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>Debate 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.</p> <p>Methods</p> <p>Mice 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.</p> <p>Results</p> <p>Overall, 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 <it>CCL3</it>, <it>CCL4</it>, <it>CXCL2</it>, and <it>MMP12 </it>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 <it>S100A8</it>, <it>S100A9 </it>and <it>MMP9</it>.</p> <p>Conclusions</p> <p>Collectively, 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.</p> |
| first_indexed | 2024-12-10T19:40:04Z |
| format | Article |
| id | doaj.art-0162fa4f3a1f4b49ac6d75840589bd45 |
| institution | Directory Open Access Journal |
| issn | 1465-9921 |
| language | English |
| last_indexed | 2024-12-10T19:40:04Z |
| publishDate | 2010-06-01 |
| publisher | BMC |
| record_format | Article |
| series | Respiratory Research |
| spelling | doaj.art-0162fa4f3a1f4b49ac6d75840589bd452022-12-22T01:36:01ZengBMCRespiratory Research1465-99212010-06-011117010.1186/1465-9921-11-70Response 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 miceAntonini James MLi ShengqiaoKashon Michael LZeidler-Erdely Patti C<p>Abstract</p> <p>Background</p> <p>Debate 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.</p> <p>Methods</p> <p>Mice 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.</p> <p>Results</p> <p>Overall, 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 <it>CCL3</it>, <it>CCL4</it>, <it>CXCL2</it>, and <it>MMP12 </it>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 <it>S100A8</it>, <it>S100A9 </it>and <it>MMP9</it>.</p> <p>Conclusions</p> <p>Collectively, 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.</p>http://respiratory-research.com/content/11/1/70 |
| spellingShingle | Antonini James M Li Shengqiao Kashon Michael L Zeidler-Erdely Patti C 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 Respiratory Research |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| url | http://respiratory-research.com/content/11/1/70 |
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