Abstract

HYPOTHESIS: We are developing the nasal lavage model as a means of studying the inflammatory response of respiratory epithelium in vivo. In preliminary studies, we have found that concentrations of the pro-inflammatory cytokine interleukin-8 (IL-8) are higher in nasal lavage fluid from CF patients than from normals. In this proposal, we plan to define the inflammatory state of the nasal mucosa more thoroughly in CF patients, then test our hypothesis that the AAT gene can be delivered to the nasal mucosa in CF subjects using plasmid/cationic liposome complexes and that expression of the AAT gene locally in respiratory epithelium will suppress inflammation.
SPECIFIC AIMS : 1) To characterize the inflammatory and protease/antiprotease state of the nasal mucosa in patients w/CF by: a)measuring in nasal lavage fluid the concentrations of inflammation-related cytokines, AAT protein and free elastase; and b) determining in nasal mucosal scrapings the numbers of inflammatory cells present and which inflammation-related cytokine genes are expressed. 2) To determine whether the AAT gene canbe delivered to the nasal mucosa of patients w/CF using cationic liposomes; to define the magnitude and time course of transgene expression; and to determine whether AAT gene expression in nasal mucosa decreases inflammation. We are currently conducting the experiments outlined in Specific Aim #1.
Specific Aim #2 will require the facilities in the GCRC.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
General Clinical Research Centers Program (M01)
Project #
5M01RR000095-40
Application #
6409572
Study Section
National Center for Research Resources Initial Review Group (RIRG)
Project Start
1977-12-01
Project End
2002-11-30
Budget Start
Budget End
Support Year
40
Fiscal Year
2000
Total Cost
Indirect Cost

  Institution

Name
Vanderbilt University Medical Center
Department
Type
DUNS #
004413456
City
Nashville
State
TN
Country
United States
Zip Code
37203

  Publications

Kaltenbach, Karol; O'Grady, Kevin E; Heil, Sarah H et al. (2018) Prenatal exposure to methadone or buprenorphine: Early childhood developmental outcomes. Drug Alcohol Depend 185:40-49
Gupta, Samir K; Yeh, Eunice; Kitch, Douglas W et al. (2017) Bone mineral density reductions after tenofovir disoproxil fumarate initiation and changes in phosphaturia: a secondary analysis of ACTG A5224s. J Antimicrob Chemother 72:2042-2048
Gilchuk, Pavlo; Knight, Frances C; Wilson, John T et al. (2017) Eliciting Epitope-Specific CD8+ T Cell Response by Immunization with Microbial Protein Antigens Formulated with ?-Galactosylceramide: Theory, Practice, and Protocols. Methods Mol Biol 1494:321-352
Sebag, Sara C; Koval, Olha M; Paschke, John D et al. (2017) Mitochondrial CaMKII inhibition in airway epithelium protects against allergic asthma. JCI Insight 2:e88297
Joy, Nino G; Mikeladze, Maia; Younk, Lisa M et al. (2016) Effects of equivalent sympathetic activation during hypoglycemia on endothelial function and pro-atherothrombotic balance in healthy individuals and obese standard treated type 2 diabetes. Metabolism 65:1695-1705
Gilchuk, Pavlo; Hill, Timothy M; Guy, Clifford et al. (2016) A Distinct Lung-Interstitium-Resident Memory CD8(+) T Cell Subset Confers Enhanced Protection to Lower Respiratory Tract Infection. Cell Rep 16:1800-9
Jones, Hendrée E; Seashore, Carl; Johnson, Elisabeth et al. (2016) Measurement of neonatal abstinence syndrome: Evaluation of short forms. J Opioid Manag 12:19-23
Laird, Chris; Burdorf, Lars; Pierson 3rd, Richard N (2016) Lung xenotransplantation: a review. Curr Opin Organ Transplant 21:272-8
Chung, C P; Ormseth, M J; Connelly, M A et al. (2016) GlycA, a novel marker of inflammation, is elevated in systemic lupus erythematosus. Lupus 25:296-300
Towse, Theodore F; Childs, Benjamin T; Sabin, Shea A et al. (2016) Comparison of muscle BOLD responses to arterial occlusion at 3 and 7 Tesla. Magn Reson Med 75:1333-40

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