Abstract

The overall goal of our research is to elucidate the role of macrophages and inflammatory mediators in acute and chronic pulmonary injury induced by vesicants with the long-term objective of identifying targets for therapeutic intervention. We hypothesize that macrophages play a dual role in the pulmonary toxicity of vesicants. Whereas initially classically activated M1 macrophages contribute to acute tissue injury by releasing excessive quantities of proinflammatory/cytotoxic mediators, subsequent release of mitogenic and fibrogenic mediators by overactive M2 macrophages leads to chronic injury including pulmonary fibrosis. Using sulfur mustard and nitrogen mustard as model vesicants, plans are to determine if M1 and M2 macrophage subpopulations differentially contribute to the acute and long-term consequences of vesicant intoxication, and if pharmacologically modifying their activity or mediators they release mitigates toxicity. Working with the Medicinal Chemistry and Pharmaceutics Core, we also plan to engineer and evaluate an injectable lung delivery system consisting of poly(ethylene glycol) hydrogel particles (

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Specialized Center--Cooperative Agreements (U54)
Project #
7U54AR055073-08
Application #
8545531
Study Section
Special Emphasis Panel (ZRG1-MDCN-J)
Project Start
Project End
Budget Start
2013-07-01
Budget End
2014-06-30
Support Year
8
Fiscal Year
2013
Total Cost
$596,214
Indirect Cost
$44,839

  Institution

Name
Rbhs-Robert Wood Johnson Medical School
Department
Type
DUNS #
078795875
City
Piscataway
State
NJ
Country
United States
Zip Code
08854

  Publications

Moretti, Alysha; Li, Qi; Chmielowski, Rebecca et al. (2018) Nanotherapeutics Containing Lithocholic Acid-Based Amphiphilic Scorpion-Like Macromolecules Reduce In Vitro Inflammation in Macrophages: Implications for Atherosclerosis. Nanomaterials (Basel) 8:
Szilagyi, John T; Fussell, Karma C; Wang, Yun et al. (2018) Quinone and nitrofurantoin redox cycling by recombinant cytochrome b5 reductase. Toxicol Appl Pharmacol 359:102-107
Joseph, Laurie B; Composto, Gabriella M; Perez, Roberto M et al. (2018) Sulfur mustard induced mast cell degranulation in mouse skin is inhibited by a novel anti-inflammatory and anticholinergic bifunctional prodrug. Toxicol Lett 293:77-81
Chang, Yoke-Chen; Gordon, Marion K; Gerecke, Donald R (2018) Expression of Laminin 332 in Vesicant Skin Injury and Wound Repair. Clin Dermatol (Wilmington) 2:
Yang, Shaojun; Jan, Yi-Hua; Mishin, Vladimir et al. (2017) Diacetyl/l-Xylulose Reductase Mediates Chemical Redox Cycling in Lung Epithelial Cells. Chem Res Toxicol 30:1406-1418
Venosa, Alessandro; Gow, James G; Hall, LeRoy et al. (2017) Regulation of Nitrogen Mustard-Induced Lung Macrophage Activation by Valproic Acid, a Histone Deacetylase Inhibitor. Toxicol Sci 157:222-234
Francis, Mary; Sun, Richard; Cervelli, Jessica A et al. (2017) Editor's Highlight: Role of Spleen-Derived Macrophages in Ozone-Induced Lung Inflammation and Injury. Toxicol Sci 155:182-195
Chmielowski, Rebecca A; Abdelhamid, Dalia S; Faig, Jonathan J et al. (2017) Athero-inflammatory nanotherapeutics: Ferulic acid-based poly(anhydride-ester) nanoparticles attenuate foam cell formation by regulating macrophage lipogenesis and reactive oxygen species generation. Acta Biomater 57:85-94
Francis, Mary; Groves, Angela M; Sun, Richard et al. (2017) Editor's Highlight: CCR2 Regulates Inflammatory Cell Accumulation in the Lung and Tissue Injury following Ozone Exposure. Toxicol Sci 155:474-484
Malaviya, Rama; Laskin, Jeffrey D; Laskin, Debra L (2017) Anti-TNF? therapy in inflammatory lung diseases. Pharmacol Ther 180:90-98

Showing the most recent 10 out of 145 publications