Abstract

The major goals of these studies are to elucidate the individual roles of COX-1 and COX-2 in normal physiology and in various pathological states. Specifically, effort within the laboratory has focused on using COX-2 deficient mouse ES cells and COX specific inhibitors to study the roles of COX-2 in endothelial cell development and aneurysm formation. Endothelial cell ifferentiation was measured immunohistochemically by the appearance of CD-31 staining cord like structures of cells and the appearance of VEGF receptors and COX-2 on Western analysis. Our studies indicated that the deficiency of COX-2 inhibited mouse ES cell differentiation into endothelial-like cells in vitro. However, studies with COX-2 selective inhibitors have indicated that the COX-2 inhibitors blocked endothelial-like cell development even in COX-2-/- ES cells, suggesting that a COX-2 independent mechanism was responsible. In addition, a mouse model to study the contributions of COX-2 to aneurysm formation is being developed and initial studies indicate that COX-2 deficiency attenuates inflammatory responses in the mouse heart and abdominal vasculature. Also, collaborative studies have demonstrated that COX-2 deficiency increased inflammatory responses in the mouse brain.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIAES021179-17
Application #
7967956
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
17
Fiscal Year
2009
Total Cost
$467,820
Indirect Cost

  Institution

Name
National Institute of Environmental Health Sciences
Department
Type
DUNS #
City
State
Country
Zip Code

  Publications

Trivedi, Darshini B; Loftin, Charles D; Clark, James et al. (2013) ?-Arrestin-2 deficiency attenuates abdominal aortic aneurysm formation in mice. Circ Res 112:1219-29
Sayers, Brian C; Taylor, Alexia J; Glista-Baker, Ellen E et al. (2013) Role of cyclooxygenase-2 in exacerbation of allergen-induced airway remodeling by multiwalled carbon nanotubes. Am J Respir Cell Mol Biol 49:525-35
Lee, Jong Kwon; Sayers, Brian C; Chun, Kyung-Soo et al. (2012) Multi-walled carbon nanotubes induce COX-2 and iNOS expression via MAP kinase-dependent and -independent mechanisms in mouse RAW264.7 macrophages. Part Fibre Toxicol 9:14
Zhang, Dan; Hu, Xiaoming; Qian, Li et al. (2009) Prostaglandin E2 released from activated microglia enhances astrocyte proliferation in vitro. Toxicol Appl Pharmacol 238:64-70