This UCLA Center comprises 3 continuing research projects centered around the key role and mechanisms by which particulate pollutants induce airway inflammation. All projects focus on oxidative stress as a central mechanism by which xenobiotics mediate adjuvant effects in allergic airway inflammation through a hierarchy of cytoprotective/anti-oxidant (Tier 1), inflammatory (Tier 2) and finally, if unchecked, cytotoxic (Tier 3) responses. Cross-cutting themes in this Center are particulate pollutants and pro-oxidative chemicals, cellular and molecular targets of oxidative stress, genetics of disease susceptibility and high responder status, development of rational interventions, and use of established human and murine models. The senior investigators, Drs. Nel, Saxon, and Diaz-Sanchez are long-term AADCRC participants. Dr. Riedl, a young translational research scientist has joined and will work with Dr. Saxon as co-project leader in a human interventional project. He brings advanced clinical research skills to this Center. Project 1 (Nel) focuses on the role of the dendritic cells as key initial participants in the biological effects of particulates. This project assesses the effects of the hierarchical oxidative stress pathways in the adjuvant effects of PM on dendritic cell function so as to initiate and drive increased Th-2 like inflammation at the interface between the innate and adaptive immune system. In Project 2 (Saxon/Riedl), 3 distinct human in vivo challenge models are used in clinical studies testing the hypothesis that induction of phase II anti-oxidant enzymes (Tier 1) leads to decreased pro-oxidative effects of DEP and thereby inhibits inflammation (Tier 2) in response to DEP-driven primary and secondary allergic responses. Project 3 (Diaz-Sanchez) extends in vivo human challenge studies with ambient fine and ultrafine particles to test the hypothesis that differences in the abilities of """"""""real life"""""""" particles to generate oxidative stress, determine inflammatory outcomes. This project will also study the genetics of PM susceptibility to particulates in high vs. low DEP responders. All projects will collaborate in a discovery process using gene array and proteomics to search for oxidative stress markers that define response type &level, susceptibility and response to therapeutic intervention. An Administrative/ Subject Recruitment/Sample Core, an Ambient Particle Collection Core, and a Proteomics core provide critical resources for all the Center's projects.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program--Cooperative Agreements (U19)
Project #
5U19AI070453-05
Application #
7888359
Study Section
Special Emphasis Panel (ZAI1-SV-I (M1))
Program Officer
Davidson, Wendy F
Project Start
2006-07-15
Project End
2012-06-30
Budget Start
2010-07-01
Budget End
2012-06-30
Support Year
5
Fiscal Year
2010
Total Cost
$1,365,876
Indirect Cost
Name
University of California Los Angeles
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
092530369
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
Heber, David; Li, Zhaoping; Garcia-Lloret, Maria et al. (2014) Sulforaphane-rich broccoli sprout extract attenuates nasal allergic response to diesel exhaust particles. Food Funct 5:35-41
Li, Ning; Wang, Meiying; Barajas, Berenice et al. (2013) Nrf2 deficiency in dendritic cells enhances the adjuvant effect of ambient ultrafine particles on allergic sensitization. J Innate Immun 5:543-54
Ooi, Aik T; Ram, Sonal; Kuo, Alan et al. (2012) Identification of an interleukin 13-induced epigenetic signature in allergic airway inflammation. Am J Transl Res 4:219-28
Li, Ning; Nel, Andre E (2011) Feasibility of biomarker studies for engineered nanoparticles: what can be learned from air pollution research. J Occup Environ Med 53:S74-9
Li, Ning; Harkema, Jack R; Lewandowski, Ryan P et al. (2010) Ambient ultrafine particles provide a strong adjuvant effect in the secondary immune response: implication for traffic-related asthma flares. Am J Physiol Lung Cell Mol Physiol 299:L374-83
Kang, Xuedong; Li, Ning; Wang, Meiying et al. (2010) Adjuvant effects of ambient particulate matter monitored by proteomics of bronchoalveolar lavage fluid. Proteomics 10:520-31
George, Saji; Pokhrel, Suman; Xia, Tian et al. (2010) Use of a rapid cytotoxicity screening approach to engineer a safer zinc oxide nanoparticle through iron doping. ACS Nano 4:15-29
Tachdjian, Raffi; Al Khatib, Shadi; Schwinglshackl, Andreas et al. (2010) In vivo regulation of the allergic response by the IL-4 receptor alpha chain immunoreceptor tyrosine-based inhibitory motif. J Allergy Clin Immunol 125:1128-1136.e8
Kovochich, Michael; Espinasse, Benjamin; Auffan, Melanie et al. (2009) Comparative toxicity of C60 aggregates toward mammalian cells: role of tetrahydrofuran (THF) decomposition. Environ Sci Technol 43:6378-84
Nel, Andre E; Mädler, Lutz; Velegol, Darrell et al. (2009) Understanding biophysicochemical interactions at the nano-bio interface. Nat Mater 8:543-57

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