Route of Arsenic Exposure Differentially Impacts the Expression of Genes Involved in Gut-Mucosa-Associated Immune Responses and Gastrointestinal Permeability
First-pass metabolism alters arsenic biotransformation and its immunomodulatory activities. This study aims to determine the mRNA expression of intestinal-immunity- and permeability-associated genes, levels of cytokine/chemokines and levels of immunoglobulin isotypes when CD-1 mice were exposed to a...
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| Format: | Article |
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MDPI AG
2023-03-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/7/6352 |
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| author | Kuppan Gokulan Aakriti Mathur Amit Kumar Michelle M. Vanlandingham Sangeeta Khare |
| author_facet | Kuppan Gokulan Aakriti Mathur Amit Kumar Michelle M. Vanlandingham Sangeeta Khare |
| author_sort | Kuppan Gokulan |
| collection | DOAJ |
| description | First-pass metabolism alters arsenic biotransformation and its immunomodulatory activities. This study aims to determine the mRNA expression of intestinal-immunity- and permeability-associated genes, levels of cytokine/chemokines and levels of immunoglobulin isotypes when CD-1 mice were exposed to a single dose of intravenous (IV) sodium arsenite (50 µg/kg body weight (BW)) and to compare these responses to exposure via oral gavage (OG) (50 µg/kg BW). Samples were collected at 1, 4, 24 and 48 h post IV exposure and 24 and 48 h post OG. Sodium arsenite IV exposure led to a transient modulation of mRNA expression and protein levels of immunity-related genes involved in inflammation/apoptotic pathways and production of cytokines/chemokines, whereas it also led to downregulated expression of genes encoding tight junction, focal adhesion, and gap junction proteins, which are responsible for maintaining cell permeability. Oral exposure perturbed fewer cell-permeability-related genes at 24 and 48 h post exposure. At 24 h post exposure, OG decreased IgA and IgG2b levels; however, IV exposure significantly increased IgG2b, IgG3 and IgA in ileal tissue. Earlier, we showed significant downregulation of mRNA expression of genes involved in the immune-related pathways during OG in the intestinal mucosa of the same animals. Cumulatively, these results provide evidence that the exposure route of a xenobiotic can differentially impact the intestinal responses due to the impact of first-pass metabolism. |
| first_indexed | 2024-03-11T05:36:24Z |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T05:36:24Z |
| publishDate | 2023-03-01 |
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| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-fc0918d9a4224d9da68b22d8b3fa14a62023-11-17T16:49:52ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-03-01247635210.3390/ijms24076352Route of Arsenic Exposure Differentially Impacts the Expression of Genes Involved in Gut-Mucosa-Associated Immune Responses and Gastrointestinal PermeabilityKuppan Gokulan0Aakriti Mathur1Amit Kumar2Michelle M. Vanlandingham3Sangeeta Khare4Division of Microbiology, National Center for Toxicological Research, US Food and Drug Administration, 3900 NCTR Rd, Jefferson, AR 72079, USADivision of Microbiology, National Center for Toxicological Research, US Food and Drug Administration, 3900 NCTR Rd, Jefferson, AR 72079, USADivision of Microbiology, National Center for Toxicological Research, US Food and Drug Administration, 3900 NCTR Rd, Jefferson, AR 72079, USADivision of Biochemical Toxicology, National Center for Toxicological Research, US Food and Drug Administration, 3900 NCTR Rd, Jefferson, AR 72079, USADivision of Microbiology, National Center for Toxicological Research, US Food and Drug Administration, 3900 NCTR Rd, Jefferson, AR 72079, USAFirst-pass metabolism alters arsenic biotransformation and its immunomodulatory activities. This study aims to determine the mRNA expression of intestinal-immunity- and permeability-associated genes, levels of cytokine/chemokines and levels of immunoglobulin isotypes when CD-1 mice were exposed to a single dose of intravenous (IV) sodium arsenite (50 µg/kg body weight (BW)) and to compare these responses to exposure via oral gavage (OG) (50 µg/kg BW). Samples were collected at 1, 4, 24 and 48 h post IV exposure and 24 and 48 h post OG. Sodium arsenite IV exposure led to a transient modulation of mRNA expression and protein levels of immunity-related genes involved in inflammation/apoptotic pathways and production of cytokines/chemokines, whereas it also led to downregulated expression of genes encoding tight junction, focal adhesion, and gap junction proteins, which are responsible for maintaining cell permeability. Oral exposure perturbed fewer cell-permeability-related genes at 24 and 48 h post exposure. At 24 h post exposure, OG decreased IgA and IgG2b levels; however, IV exposure significantly increased IgG2b, IgG3 and IgA in ileal tissue. Earlier, we showed significant downregulation of mRNA expression of genes involved in the immune-related pathways during OG in the intestinal mucosa of the same animals. Cumulatively, these results provide evidence that the exposure route of a xenobiotic can differentially impact the intestinal responses due to the impact of first-pass metabolism.https://www.mdpi.com/1422-0067/24/7/6352arsenicintravenousexposure routeimmunityintestinemucosa |
| spellingShingle | Kuppan Gokulan Aakriti Mathur Amit Kumar Michelle M. Vanlandingham Sangeeta Khare Route of Arsenic Exposure Differentially Impacts the Expression of Genes Involved in Gut-Mucosa-Associated Immune Responses and Gastrointestinal Permeability International Journal of Molecular Sciences arsenic intravenous exposure route immunity intestine mucosa |
| title | Route of Arsenic Exposure Differentially Impacts the Expression of Genes Involved in Gut-Mucosa-Associated Immune Responses and Gastrointestinal Permeability |
| title_full | Route of Arsenic Exposure Differentially Impacts the Expression of Genes Involved in Gut-Mucosa-Associated Immune Responses and Gastrointestinal Permeability |
| title_fullStr | Route of Arsenic Exposure Differentially Impacts the Expression of Genes Involved in Gut-Mucosa-Associated Immune Responses and Gastrointestinal Permeability |
| title_full_unstemmed | Route of Arsenic Exposure Differentially Impacts the Expression of Genes Involved in Gut-Mucosa-Associated Immune Responses and Gastrointestinal Permeability |
| title_short | Route of Arsenic Exposure Differentially Impacts the Expression of Genes Involved in Gut-Mucosa-Associated Immune Responses and Gastrointestinal Permeability |
| title_sort | route of arsenic exposure differentially impacts the expression of genes involved in gut mucosa associated immune responses and gastrointestinal permeability |
| topic | arsenic intravenous exposure route immunity intestine mucosa |
| url | https://www.mdpi.com/1422-0067/24/7/6352 |
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