Balancing anti-inflammatory and anti-oxidant responses in murine bone marrow derived macrophages.
<h4>Rationale</h4>The underlying pathophysiology of bronchopulmonary dysplasia includes a macrophage-mediated host response orchestrated by anti-inflammatory peroxisome proliferator-activated receptor gamma (PPARγ) and anti-oxidant nuclear factor (erythroid-derived 2)-like 2 (Nrf2). Thes...
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Public Library of Science (PLoS)
2017-01-01
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| author | Christopher R Nitkin Tracey L Bonfield |
| author_facet | Christopher R Nitkin Tracey L Bonfield |
| author_sort | Christopher R Nitkin |
| collection | DOAJ |
| description | <h4>Rationale</h4>The underlying pathophysiology of bronchopulmonary dysplasia includes a macrophage-mediated host response orchestrated by anti-inflammatory peroxisome proliferator-activated receptor gamma (PPARγ) and anti-oxidant nuclear factor (erythroid-derived 2)-like 2 (Nrf2). These have not yet been studied in combination. This study tested the hypothesis that combined inflammatory and oxidative stressors would interact and change PPARγ- and Nrf2-regulated gene expression and antioxidant capacity. Therefore, we investigated the effect of dual stimulation with lipopolysaccharide and hyperoxia in murine bone marrow-derived macrophages (BMDM).<h4>Methods</h4>Sub-confluent BMDM from wild-type C57BL/6J mice were treated with lipopolysaccharide (LPS) 1ug/mL for 2 hours followed by room air (21% oxygen) or hyperoxia (95% oxygen) for 24 hours. Taqman real time-polymerase chain reaction gene expression assays, total antioxidant capacity assays, and Luminex assays were performed.<h4>Results</h4>Supernatants of cultured BMDM contained significant antioxidant capacity. In room air, LPS treatment decreased expression of PPARγ and Nrf2, and increased expression of tumor necrosis factor-alpha and heme oxygenase-1; similar findings were observed under hyperoxic conditions. LPS treatment decreased cellular total antioxidant capacity in room air but not in hyperoxia. Increased expression of sulfiredoxin-1 in response to hyperoxia was not observed in LPS-treated cells. Dual stimulation with LPS treatment and exposure to hyperoxia did not have synergistic effects on gene expression. Cellular total antioxidant capacity was not changed by hyperoxia exposure.<h4>Conclusions</h4>Our hypothesis was supported and we demonstrate an interaction between inflammatory and oxidative stressors in a model system of bronchopulmonary dysplasia pathogenesis. The protective anti-oxidant effect of cell culture media may have protected the cells from the most deleterious effects of hyperoxia. |
| format | Article |
| id | doaj-art-589e93700a36497db9e61379b3676234 |
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| issn | 1932-6203 |
| language | English |
| publishDate | 2017-01-01 |
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| spelling | doaj-art-589e93700a36497db9e61379b36762342025-08-20T02:45:29ZengPublic Library of Science (PLoS)PLoS ONE1932-62032017-01-01129e018446910.1371/journal.pone.0184469Balancing anti-inflammatory and anti-oxidant responses in murine bone marrow derived macrophages.Christopher R NitkinTracey L Bonfield<h4>Rationale</h4>The underlying pathophysiology of bronchopulmonary dysplasia includes a macrophage-mediated host response orchestrated by anti-inflammatory peroxisome proliferator-activated receptor gamma (PPARγ) and anti-oxidant nuclear factor (erythroid-derived 2)-like 2 (Nrf2). These have not yet been studied in combination. This study tested the hypothesis that combined inflammatory and oxidative stressors would interact and change PPARγ- and Nrf2-regulated gene expression and antioxidant capacity. Therefore, we investigated the effect of dual stimulation with lipopolysaccharide and hyperoxia in murine bone marrow-derived macrophages (BMDM).<h4>Methods</h4>Sub-confluent BMDM from wild-type C57BL/6J mice were treated with lipopolysaccharide (LPS) 1ug/mL for 2 hours followed by room air (21% oxygen) or hyperoxia (95% oxygen) for 24 hours. Taqman real time-polymerase chain reaction gene expression assays, total antioxidant capacity assays, and Luminex assays were performed.<h4>Results</h4>Supernatants of cultured BMDM contained significant antioxidant capacity. In room air, LPS treatment decreased expression of PPARγ and Nrf2, and increased expression of tumor necrosis factor-alpha and heme oxygenase-1; similar findings were observed under hyperoxic conditions. LPS treatment decreased cellular total antioxidant capacity in room air but not in hyperoxia. Increased expression of sulfiredoxin-1 in response to hyperoxia was not observed in LPS-treated cells. Dual stimulation with LPS treatment and exposure to hyperoxia did not have synergistic effects on gene expression. Cellular total antioxidant capacity was not changed by hyperoxia exposure.<h4>Conclusions</h4>Our hypothesis was supported and we demonstrate an interaction between inflammatory and oxidative stressors in a model system of bronchopulmonary dysplasia pathogenesis. The protective anti-oxidant effect of cell culture media may have protected the cells from the most deleterious effects of hyperoxia.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0184469&type=printable |
| spellingShingle | Christopher R Nitkin Tracey L Bonfield Balancing anti-inflammatory and anti-oxidant responses in murine bone marrow derived macrophages. PLoS ONE |
| title | Balancing anti-inflammatory and anti-oxidant responses in murine bone marrow derived macrophages. |
| title_full | Balancing anti-inflammatory and anti-oxidant responses in murine bone marrow derived macrophages. |
| title_fullStr | Balancing anti-inflammatory and anti-oxidant responses in murine bone marrow derived macrophages. |
| title_full_unstemmed | Balancing anti-inflammatory and anti-oxidant responses in murine bone marrow derived macrophages. |
| title_short | Balancing anti-inflammatory and anti-oxidant responses in murine bone marrow derived macrophages. |
| title_sort | balancing anti inflammatory and anti oxidant responses in murine bone marrow derived macrophages |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0184469&type=printable |
| work_keys_str_mv | AT christopherrnitkin balancingantiinflammatoryandantioxidantresponsesinmurinebonemarrowderivedmacrophages AT traceylbonfield balancingantiinflammatoryandantioxidantresponsesinmurinebonemarrowderivedmacrophages |