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 (

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
Name
Rbhs-Robert Wood Johnson Medical School
Department
Type
DUNS #
078795875
City
Piscataway
State
NJ
Country
United States
Zip Code
08854
Lasfar, Ahmed; de la Torre, Andrew; Abushahba, Walid et al. (2016) Concerted action of IFN-α and IFN-λ induces local NK cell immunity and halts cancer growth. Oncotarget :
Composto, Gabriella M; Laskin, Jeffrey D; Laskin, Debra L et al. (2016) Mitigation of nitrogen mustard mediated skin injury by a novel indomethacin bifunctional prodrug. Exp Mol Pathol 100:522-31
Gordon, Marion K; DeSantis-Rodrigues, Andrea; Hahn, Rita et al. (2016) The molecules in the corneal basement membrane zone affected by mustard exposure suggest potential therapies. Ann N Y Acad Sci 1378:158-165
Udasin, Ronald G; Wen, Xia; Bircsak, Kristin M et al. (2016) Nrf2 Regulates the Sensitivity of Mouse Keratinocytes to Nitrogen Mustard via Multidrug Resistance-Associated Protein 1 (Mrp1). Toxicol Sci 149:202-12
Francis, Mary; Sun, Richard; Cervelli, Jessica A et al. (2016) Role of Spleen-derived Macrophages in Ozone-Induced Lung Inflammation and Injury. Toxicol Sci :
Weinberger, Barry; Malaviya, Rama; Sunil, Vasanthi R et al. (2016) Mustard vesicant-induced lung injury: Advances in therapy. Toxicol Appl Pharmacol 305:1-11
Businaro, Rita; Corsi, Mariangela; Di Raimo, Tania et al. (2016) Multidisciplinary approaches to stimulate wound healing. Ann N Y Acad Sci 1378:137-142
Venosa, Alessandro; Malaviya, Rama; Choi, Hyejeong et al. (2016) Characterization of Distinct Macrophage Subpopulations during Nitrogen Mustard-Induced Lung Injury and Fibrosis. Am J Respir Cell Mol Biol 54:436-46
Mandal, Mili; Gardner, Carol R; Sun, Richard et al. (2016) The spleen as an extramedullary source of inflammatory cells responding to acetaminophen-induced liver injury. Toxicol Appl Pharmacol 304:110-20
Jan, Yi-Hua; Richardson, Jason R; Baker, Angela A et al. (2016) Novel approaches to mitigating parathion toxicity: targeting cytochrome P450-mediated metabolism with menadione. Ann N Y Acad Sci 1378:80-86

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