Farnesoid X receptor regulates macrophage activation and recruitment to the lung following exposure of mice to nitrogen mustard
| العنوان: | Farnesoid X receptor regulates macrophage activation and recruitment to the lung following exposure of mice to nitrogen mustard |
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| المؤلفون: | Tanvi Banota, Alexa Murray, Amanda Sowinski, Bo Kong, Grace L Guo, Jeffrey D Laskin, Debra L Laskin |
| المصدر: | The Journal of Immunology. 206:11.12-11.12 |
| بيانات النشر: | The American Association of Immunologists, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Immunology, Immunology and Allergy |
| الوصف: | Nitrogen mustard (NM) is a toxic vesicant known to cause acute lung injury which progresses to fibrosis. This is accompanied by the accumulation of pro-inflammatory/cytotoxic M1 macrophages and anti-inflammatory/pro-fibrotic M2 macrophages in the lung. Farnesoid X receptor (FXR) is a bile-acid activated nuclear receptor involved in lipid homeostasis; it has also been shown to exert anti-inflammatory activity. In these studies, we analyzed the role of FXR in regulating macrophage accumulation and activation in the lung following NM exposure. Male and female wild type (WT) and FXR−/− mice were treated with PBS (control) or NM (0.08 mg/kg) via intratracheal instillation. Lung tissue and bronchoalveolar lavage (BAL) fluid were collected 3, 14, and 28 days later. NM caused histopathologic alterations in the lung including inflammatory cell infiltration, septal damage, and epithelial thickening, which were more prominent in FXR−/− mice relative to WT mice at all post exposure time points. This correlated with aggravated increases in BAL protein and cell content. Flow cytometric analysis revealed pro-inflammatory macrophages were most abundant in BAL 3 days post NM, a response more pronounced in FXR−/− mice. In male but not female mice, increases in proinflammatory macrophages persisted in the lung for at least 28 d post NM. In contrast, while anti-inflammatory macrophages also increased in the lung following NM administration, no differences were observed between WT and FXR−/− mice. These findings demonstrate that FXR modulates proinflammatory macrophage responses to NM in a sex-dependent manner and suggest a potential new target for the development of therapeutics to blunt mustard vesicant induced lung inflammation and injury. |
| تدمد: | 1550-6606 0022-1767 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_________::540494941808695c19f436b5bf45659eTest https://doi.org/10.4049/jimmunol.206.supp.11.12Test |
| رقم الانضمام: | edsair.doi...........540494941808695c19f436b5bf45659e |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15506606 00221767 |
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