Abstract

The long term objectives of the proposed studies are to precisely define specific interactions between host cells and their secreted factors with the opportunistic bacterial pathogen, Pseudomonas aeruginosa (PA). Knowledge of these interactions and their sequelae will provide information critical to rational development of therapies to lessen or prevent the consequences of corneal inflammation which often lead to visual impairment. A single hypothesis will be tested: That appropriate regulation of immune cells, chemokines, and cytokines and an effective, controlled early host inflammatory (e.g., PMN) response determines whether or not PA keratitis is resolved and whether vision is restored or lost.
Specific aims to test the above hypothesis are:
Aim 1. To characterize the role of specific CXC and CC chemokines in the inflammatory response to PA ocular infection in genetically and aged susceptible vs. resistant inbred mice.
Aim 2. To characterize the role of specific cytokines in the inflammatory response to PA ocular; infection in susceptible and resistant mouse models.
Aim 3. To determine the role of specific cells [macrophages, PMNs, T cells, and Langerhans cells (LC)] in PA ocular infection in susceptible and resistant mouse models. To achieve these aims, molecular microbiological, immunological and biochemical methods will be used.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY002986-23
Application #
6384304
Study Section
Visual Sciences A Study Section (VISA)
Program Officer
Fisher, Richard S
Project Start
1979-04-01
Project End
2004-03-31
Budget Start
2001-04-01
Budget End
2002-03-31
Support Year
23
Fiscal Year
2001
Total Cost
$282,112
Indirect Cost

  Institution

Name
Wayne State University
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
City
Detroit
State
MI
Country
United States
Zip Code
48202

  Publications

McClellan, Sharon A; Ekanayaka, Sandamali A; Li, Cui et al. (2015) Thrombomodulin Protects Against Bacterial Keratitis, Is Anti-Inflammatory, but Not Angiogenic. Invest Ophthalmol Vis Sci 56:8091-100
McClellan, Sharon; Jiang, Xiaoyu; Barrett, Ronald et al. (2015) High-mobility group box 1: a novel target for treatment of Pseudomonas aeruginosa keratitis. J Immunol 194:1776-87
Jiang, Xiaoyu; McClellan, Sharon A; Barrett, Ronald et al. (2014) HGF signaling impacts severity of Pseudomonas aeruginosa keratitis. Invest Ophthalmol Vis Sci 55:2180-90
Li, Cui; McClellan, Sharon A; Barrett, Ronald et al. (2014) Interleukin 17 regulates Mer tyrosine kinase-positive cells in Pseudomonas aeruginosa keratitis. Invest Ophthalmol Vis Sci 55:6886-900
Hazlett, Linda D; Jiang, Xiaoyu; McClellan, Sharon A (2014) IL-10 function, regulation, and in bacterial keratitis. J Ocul Pharmacol Ther 30:373-80
Foldenauer, Megan E B; McClellan, Sharon A; Berger, Elizabeth A et al. (2013) Mammalian target of rapamycin regulates IL-10 and resistance to Pseudomonas aeruginosa corneal infection. J Immunol 190:5649-58
Berger, Elizabeth A; McClellan, Sharon A; Vistisen, Kerry S et al. (2013) HIF-1? is essential for effective PMN bacterial killing, antimicrobial peptide production and apoptosis in Pseudomonas aeruginosa keratitis. PLoS Pathog 9:e1003457
Berger, Elizabeth A; Vistisen, Kerry S; Barrett, Ronald P et al. (2012) Effects of VIP on corneal reconstitution and homeostasis following Pseudomonas aeruginosa induced keratitis. Invest Ophthalmol Vis Sci 53:7432-9
Jiang, Xiaoyu; McClellan, Sharon A; Barrett, Ronald P et al. (2012) The role of VIP in cornea. Invest Ophthalmol Vis Sci 53:7560-6
Foldenauer, Megan E B; McClellan, Sharon A; Barrett, Ronald P et al. (2012) Substance P affects growth factors in Pseudomonas aeruginosa-infected mouse cornea. Cornea 31:1176-88

Showing the most recent 10 out of 111 publications