Abstract

The goal of this proposal is to understand interactions between intestinal epithelial cells and neutrophils that occurs during intestinal inflammation. An approach has been used with in vitro epithelial monolayers and peripheral blood neutrophils. The specific new aims are to determine the compartment in neutrophils which release 5' AMP and study the biology of the epithelial ectoenzyme CD73 and receptor A2b for adenosine. Second, studies of the role of CD47 in epithelial cell neutrophil interactions will be studied by overexpressing CD47 in epithelial cells and expressing dominant negative mutants. A novel epithelial ligand will be defined, and finally the role of intraepithelial lymphocytes will be defined in a mixed cell culture system.
The third aim will be to identify novel factors expressed during bacterial infection of epithelial cells, and finally the ability of long acting analogs of lipoxins to inhibit neutrophil interactions and murine colitis will be studied.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK047662-09
Application #
6177060
Study Section
General Medicine A Subcommittee 2 (GMA)
Program Officer
Hamilton, Frank A
Project Start
1993-09-30
Project End
2002-08-31
Budget Start
2000-09-01
Budget End
2001-08-31
Support Year
9
Fiscal Year
2000
Total Cost
$295,450
Indirect Cost

  Institution

Name
Emory University
Department
Pathology
Type
Schools of Medicine
DUNS #
042250712
City
Atlanta
State
GA
Country
United States
Zip Code
30322

  Publications

Szeto, Frances L; Sun, Jun; Kong, Juan et al. (2007) Involvement of the vitamin D receptor in the regulation of NF-kappaB activity in fibroblasts. J Steroid Biochem Mol Biol 103:563-6
Duan, Yingli; Liao, Anne P; Kuppireddi, Sumalatha et al. (2007) beta-Catenin activity negatively regulates bacteria-induced inflammation. Lab Invest 87:613-24
Sun, Jun; Fegan, Pamela E; Desai, Anjali S et al. (2007) Flagellin-induced tolerance of the Toll-like receptor 5 signaling pathway in polarized intestinal epithelial cells. Am J Physiol Gastrointest Liver Physiol 292:G767-78
Sun, Jun; Kong, Juan; Duan, Yingli et al. (2006) Increased NF-kappaB activity in fibroblasts lacking the vitamin D receptor. Am J Physiol Endocrinol Metab 291:E315-22
Sun, Jun; Hobert, Michael E; Duan, Yingli et al. (2005) Crosstalk between NF-kappaB and beta-catenin pathways in bacterial-colonized intestinal epithelial cells. Am J Physiol Gastrointest Liver Physiol 289:G129-37
Sun, Jun; Hobert, Michael E; Rao, Anjali S et al. (2004) Bacterial activation of beta-catenin signaling in human epithelia. Am J Physiol Gastrointest Liver Physiol 287:G220-7
Lin, Patricia W; Simon Jr, Peter O; Gewirtz, Andrew T et al. (2004) Paneth cell cryptdins act in vitro as apical paracrine regulators of the innate inflammatory response. J Biol Chem 279:19902-7
Kucharzik, Torsten; Gewirtz, Andrew T; Merlin, Didier et al. (2003) Lateral membrane LXA4 receptors mediate LXA4's anti-inflammatory actions on intestinal epithelium. Am J Physiol Cell Physiol 284:C888-96
Yan, Yiping; Dempsey, Robert J; Flemmer, Andreas et al. (2003) Inhibition of Na(+)-K(+)-Cl(-) cotransporter during focal cerebral ischemia decreases edema and neuronal damage. Brain Res 961:22-31
Gewirtz, Andrew T; Collier-Hyams, Lauren S; Young, Andrew N et al. (2002) Lipoxin a4 analogs attenuate induction of intestinal epithelial proinflammatory gene expression and reduce the severity of dextran sodium sulfate-induced colitis. J Immunol 168:5260-7

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