Abstract

and specific aims): This project proposes to define the role of the interleukin-1 type II receptor (IL-1 IIr) in neutrophil recruitment to lung tissue during inflammation. An in vitro model using relevant rat lung cells will be studied to determine the influence IL-1b neutralization via gene delivery has on cytokine induced neutrophil chemottractant (CINC) chemokine production and neutrophil chemotaxis. Additionally, the utility of IL-1 Iir gene expression in vivo in an acute neutrophilic alveolitis model in rat lung will be explored.
The specific aims are: 1) to induce the production of soluble IL-1 IIr protein in relevant rat lung cells in culture by delivery of the human IL-1 IIr gene; 2) to determine if over-expression of soluble IL-1 IIr can inhibit IL-1b mediated chemotaxis of neutrophils in vitro; and 3) to over-express IL-1 IIr in lung tissue in vivo and test the influence on neutrophil migration into lung tissue following endotoxin challenge.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Academic Research Enhancement Awards (AREA) (R15)
Project #
1R15HL056336-01
Application #
2234906
Study Section
Lung Biology and Pathology Study Section (LBPA)
Project Start
1996-09-01
Project End
1999-08-31
Budget Start
1996-09-01
Budget End
1999-08-31
Support Year
1
Fiscal Year
1996
Total Cost
Indirect Cost

  Institution

Name
Ohio State University
Department
Type
Schools of Pharmacy
DUNS #
098987217
City
Columbus
State
OH
Country
United States
Zip Code
43210

  Publications

Lai, Ju-Ping; Bao, Shengying; Davis, Ian C et al. (2009) Inhibition of the phosphatase PTEN protects mice against oleic acid-induced acute lung injury. Br J Pharmacol 156:189-200
Lai, J-P; Dalton, J T; Knoell, D L (2007) Phosphatase and tensin homologue deleted on chromosome ten (PTEN) as a molecular target in lung epithelial wound repair. Br J Pharmacol 152:1172-84
Bao, Shenying; Knoell, Daren L (2006) Zinc modulates airway epithelium susceptibility to death receptor-mediated apoptosis. Am J Physiol Lung Cell Mol Physiol 290:L433-41
Bao, Shenying; Knoell, Daren L (2006) Zinc modulates cytokine-induced lung epithelial cell barrier permeability. Am J Physiol Lung Cell Mol Physiol 291:L1132-41
Bao, Shenying; Wang, Yijie; Sweeney, Patricia et al. (2005) Keratinocyte growth factor induces Akt kinase activity and inhibits Fas-mediated apoptosis in A549 lung epithelial cells. Am J Physiol Lung Cell Mol Physiol 288:L36-42
Coulter, Kristin R; Doseff, Andrea; Sweeney, Patricia et al. (2002) Opposing effect by cytokines on Fas-mediated apoptosis in A549 lung epithelial cells. Am J Respir Cell Mol Biol 26:58-66
Swaan, P W; Knoell, D L; Helsper, F et al. (2001) Sequential processing of human ProIL-1beta by caspase-1 and subsequent folding determined by a combined in vitro and in silico approach. Pharm Res 18:1083-90
Coulter, K R; Wewers, M D; Lowe, M P et al. (1999) Extracellular regulation of interleukin (IL)-1beta through lung epithelial cells and defective IL-1 type II receptor expression. Am J Respir Cell Mol Biol 20:964-75
Knoell, D L; Ralston, D R; Coulter, K R et al. (1998) Alpha 1-antitrypsin and protease complexation is induced by lipopolysaccharide, interleukin-1beta, and tumor necrosis factor-alpha in monocytes. Am J Respir Crit Care Med 157:246-55