In this proposal, the investigator will test the hypothesis that cytokines IL-1b and TNF-a govern COX-2 gene expression via the transcription factor nuclear factor-kB (NF-kB). Using amnion-derived WISH cells as a model system, they will examine whether NF-kB is activated following cytokine challenge. In addition, they will determine whether cytokine treatment leads to phosphorylation and degradation of 1kBa, the inhibitor protein bound to inactive NF-kB, as part of the activation process. Antisense strategies will be employed to determine the effect of ablating NF-kB subunits on COX-2 inducibility by cytokines. The proposal will also use a murine model of PTL induced by endotoxin to explore whether NF-kB activation of the COX-2 gene functions in vivo. Finally, the investigator will test the hypothesis by examining whether nuclear extracts from intrauterine tissues obtained from women in PTL contain activated NF-kB compared with tissues from women of the same gestational age but not in labor.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD035881-03
Application #
6164924
Study Section
Human Embryology and Development Subcommittee 1 (HED)
Program Officer
Ilekis, John V
Project Start
1998-03-01
Project End
2002-02-28
Budget Start
2000-03-01
Budget End
2001-02-28
Support Year
3
Fiscal Year
2000
Total Cost
$243,756
Indirect Cost
Name
Ohio State University
Department
Obstetrics & Gynecology
Type
Schools of Medicine
DUNS #
098987217
City
Columbus
State
OH
Country
United States
Zip Code
43210
Ackerman 4th, William E; Robinson, John M; Kniss, Douglas A (2005) Despite transcriptional and functional coordination, cyclooxygenase-2 and microsomal prostaglandin E synthase-1 largely reside in distinct lipid microdomains in WISH epithelial cells. J Histochem Cytochem 53:1391-401
Ackerman 4th, William E; Zhang, Xiaolan L; Rovin, Brad H et al. (2005) Modulation of cytokine-induced cyclooxygenase 2 expression by PPARG ligands through NFkappaB signal disruption in human WISH and amnion cells. Biol Reprod 73:527-35
Ackerman 4th, William E; Rovin, Brad H; Kniss, Douglas A (2004) Epidermal growth factor and interleukin-1beta utilize divergent signaling pathways to synergistically upregulate cyclooxygenase-2 gene expression in human amnion-derived WISH cells. Biol Reprod 71:2079-86
Dunn-Albanese, Lisa R; Ackerman 4th, William E; Xie, Yubing et al. (2004) Reciprocal expression of peroxisome proliferator-activated receptor-gamma and cyclooxygenase-2 in human term parturition. Am J Obstet Gynecol 190:809-16
Kniss, D A; Xie, Y; Li, Y et al. (2002) ED(27) trophoblast-like cells isolated from first-trimester chorionic villi are genetically identical to HeLa cells yet exhibit a distinct phenotype. Placenta 23:32-43
Xie, Yubing; Sproule, Taryn; Li, Yan et al. (2002) Nanoscale modifications of PET polymer surfaces via oxygen-plasma discharge yield minimal changes in attachment and growth of mammalian epithelial and mesenchymal cells in vitro. J Biomed Mater Res 61:234-45
Kniss, D A (1999) Cyclooxygenases in reproductive medicine and biology. J Soc Gynecol Investig 6:285-92