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973 results on '"Laskin, Jeffrey D."'

13. Transcriptional profiling of lung macrophages following ozone exposure in mice identifies signaling pathways regulating immunometabolic activation.

Author

Smith, Ley Cody, Abramova, Elena, Vayas, Kinal, Rodriguez, Jessica, Gelfand-Titiyevksiy, Benjamin, Roepke, Troy A, Laskin, Jeffrey D, Gow, Andrew J, and Laskin, Debra L

Subjects
CYCLIN-dependent kinase inhibitors, CELL cycle, MACROPHAGE activation, OXIDATIVE phosphorylation, TRANSCRIPTION factors, ESTROGEN receptors, CELL cycle regulation
Abstract

Macrophages play a key role in ozone-induced lung injury by regulating both the initiation and resolution of inflammation. These distinct activities are mediated by pro-inflammatory and anti-inflammatory/proresolution macrophages which sequentially accumulate in injured tissues. Macrophage activation is dependent, in part, on intracellular metabolism. Herein, we used RNA-sequencing (seq) to identify signaling pathways regulating macrophage immunometabolic activity following exposure of mice to ozone (0.8 ppm, 3 h) or air control. Analysis of lung macrophages using an Agilent Seahorse showed that inhalation of ozone increased macrophage glycolytic activity and oxidative phosphorylation at 24 and 72 h post-exposure. An increase in the percentage of macrophages in S phase of the cell cycle was observed 24 h post ozone. RNA-seq revealed significant enrichment of pathways involved in innate immune signaling and cytokine production among differentially expressed genes at both 24 and 72 h after ozone, whereas pathways involved in cell cycle regulation were upregulated at 24 h and intracellular metabolism at 72 h. An interaction network analysis identified tumor suppressor 53 (TP53), E2F family of transcription factors (E2Fs), cyclin-dependent kinase inhibitor 1A (CDKN1a/p21), and cyclin D1 (CCND1) as upstream regulators of cell cycle pathways at 24 h and TP53, nuclear receptor subfamily 4 group a member 1 (NR4A1/Nur77), and estrogen receptor alpha (ESR1/ERα) as central upstream regulators of mitochondrial respiration pathways at 72 h. To assess whether ERα regulates metabolic activity, we used ERα−/− mice. In both air and ozone-exposed mice, loss of ERα resulted in increases in glycolytic capacity and glycolytic reserve in lung macrophages with no effect on mitochondrial oxidative phosphorylation. Taken together, these results highlight the complex interaction between cell cycle, intracellular metabolism, and macrophage activation which may be important in the initiation and resolution of inflammation following ozone exposure. [ABSTRACT FROM AUTHOR]

Published
2024
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14. Repurposing FDA‐approved drugs to treat chemical weapon toxicities: Interactive case studies for trainees.

Author

Aleksunes, Lauren M., Gray, Joshua P., Meshanni, Jaclynn, Laskin, Jeffrey D., and Laskin, Debra L.

Subjects
CHEMICAL weapons, SCHOLARSHIPS, DRUG repositioning, DRUG development, DRUG efficacy
Abstract

The risk of a terrorist attack in the United States has created challenges on how to effectively treat toxicities that result from exposure to chemical weapons. To address this concern, the United States has organized a trans‐agency initiative across academia, government, and industry to identify drugs to treat tissue injury resulting from exposure to chemical threat agents. We sought to develop and evaluate an interactive educational session that provides hands‐on instruction on how to repurpose FDA‐approved drugs as therapeutics to treat toxicity from exposure to chemical weapons. As part of the Rutgers Summer Undergraduate Research Fellowship program, 23 undergraduate students participated in a 2‐h session that included: (1) an overview of chemical weapon toxicities, (2) a primer on pharmacology principles, and (3) an interactive session where groups of students were provided lists of FDA‐approved drugs to evaluate potential mechanisms of action and suitability as countermeasures for four chemical weapon case scenarios. The interactive session culminated in a competition for the best grant "sales pitch." From this interactive training, students improved their understanding of (1) the ability of chemical weapons to cause long‐term toxicities, (2) impact of route of administration and exposure scenario on drug efficacy, and (3) re‐purposing FDA‐approved drugs to treat disease from chemical weapon exposure. These findings demonstrated that an interactive training exercise can provide students with new insights into drug development for chemical threat agent toxicities. [ABSTRACT FROM AUTHOR]

Published
2024
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15. Effects of ozone exposure on lung injury, inflammation, and oxidative stress in a murine model of nonpneumonic endotoxemia.

Author

Radbel, Jared, Meshanni, Jaclynn A, Vayas, Kinal N, Le-Hoang, Oahn, Abramova, Elena, Zhou, Peihong, Joseph, Laurie B, Laskin, Jeffrey D, Gow, Andrew J, and Laskin, Debra L

Subjects
ADVANCED glycation end-products, ADULT respiratory distress syndrome, PULMONARY surfactant-associated protein D, ALVEOLAR macrophages, INTRAVENOUS therapy, ENDOTOXINS
Abstract

Recent studies have identified exposure to environmental levels of ozone as a risk factor for the development of acute respiratory distress syndrome (ARDS), a severe form of acute lung injury (ALI) that can develop in humans with sepsis. The aim of this study was to develop a murine model of ALI to mechanistically explore the impact of ozone exposure on ARDS development. Mice were exposed to ozone (0.8 ppm, 3 h) or air control followed 24 h later by intravenous administration of 3 mg/kg lipopolysaccharide (LPS) or PBS. Exposure of mice to ozone + LPS caused alveolar hyperplasia; increased BAL levels of albumin, IgM, phospholipids, and proinflammatory mediators including surfactant protein D and soluble receptor for advanced glycation end products were also detected in BAL, along with markers of oxidative and nitrosative stress. Administration of ozone + LPS resulted in an increase in neutrophils and anti-inflammatory macrophages in the lung, with no effects on proinflammatory macrophages. Conversely, the numbers of resident alveolar macrophages decreased after ozone + LPS; however, expression of Nos2 , Arg1 , Cxcl1 , Cxcl2 , Ccl2 by these cells increased, indicating that they are activated. These findings demonstrate that ozone sensitizes the lung to respond to endotoxin, resulting in ALI, oxidative stress, and exacerbated pulmonary inflammation, and provide support for the epidemiologic association between ozone exposure and ARDS incidence. [ABSTRACT FROM AUTHOR]

Published
2024
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36. Mustard Vesicants

Author

Malaviya, Rama, primary, E. Heck, Diane, additional, Casillas, Robert P., additional, Laskin, Jeffrey D., additional, and Laskin, Debra L., additional

Published
2019
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38. Role of PPARγ in dyslipidemia and altered pulmonary functioning in mice following ozone exposure

Author

Cody Smith, L, primary, Gow, Andrew J, additional, Abramova, Elena, additional, Vayas, Kinal, additional, Guo, Changjiang, additional, Noto, Jack, additional, Lyman, Jack, additional, Rodriquez, Jessica, additional, Gelfand-Titiyevskiy, Benjamin, additional, Malcolm, Callum, additional, Laskin, Jeffrey D, additional, and Laskin, Debra L, additional

Published
2023
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