This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.Asthma, in incurable illness affecting 7% of the population, is defined as a chronic inflammatory disorder of the airways. Eosinophils (EOS) are considered the main effector cells that prolong the underlying airway inflammatory component pathologically classified as a chronic desquamating eosinophilic bronchitis. Though current therapies are effective for some patients, there is an identified need for development of new treatments. The focus of these proposed investigations is the identification of target processes that may be developed as EOS-specific mechanism-based therapeutics designed to interrupt EOS-mediated events. Inflammation resolving mechanisms would remain intact and permanent tissue damage/destruction would be circumvented. Proposal Hypothesis The airway epithelium is a major source of the eotaxins, a family of eosinophil-selective cytokines that direct multiple proinflammatory events at sites of allergy/inflammation. Airway epithelium-derived eotaxins are an important target for development of mechanism-based antisense oligonucleotide adjunctive therapies designed to interrupt the eosinophil-mediated underlying chronic inflammation in allergic and inflammatory disorders. Molecular Biology and Imaging facility flow cytometry, fluorescence/confocal microscopy and gel documentation instrumentation will be used to test the proposed hypothesis according to the following specific aims:
specific aim 1 Explore the anti- or pro-inflammatory signals which modulate the synthesis and release of eotaxin (CCL11), eotaxin-2 (CCL24) and eotaxin-3 (CCL26) from airway epithelial cells (AEC);
specific aim 2 Explore the autocrine regulation of CCL11, CCL24 and CCL26 on the AEC eotaxin CCR3 chemokine receptor;
and specific aim 3 Investigate CCL11, CCL24 and CCL26 antisense ODN uptake, cytotoxicity and function in AEC. Successful completion of these investigations will further knowledge of the specific signaling molecules which regulate EOS adhesion, priming/activation, and delay of programmed cell death. Reduction/activation of these signals may ameliorate eosinophil-induced inflammatory tissue injury and promote resolution.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Research Centers in Minority Institutions Award (G12)
Project #
2G12RR003020-24
Application #
7715255
Study Section
Special Emphasis Panel (ZRR1-RI-3 (01))
Project Start
2008-06-01
Project End
2009-05-31
Budget Start
2008-06-01
Budget End
2009-05-31
Support Year
24
Fiscal Year
2008
Total Cost
$137,257
Indirect Cost
Name
Florida Agricultural and Mechanical University
Department
Pharmacology
Type
Schools of Pharmacy
DUNS #
623751831
City
Tallahassee
State
FL
Country
United States
Zip Code
32307
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