Abstract

of Work: Mice deficient in both COX-1 and COX-2 have been produced. These mice are being used to determine the physiological roles of the individual COX isoforms and to elucidate the ways in which the two isoforms act individually or in conjunction. Mice deficient in both isoforms die shortly after birth of patent ductus arteriosus, but otherwise appear developmentally normal. We have found that COX-2 is the isoform primarily responsible for the closure of the ductus and that COX-2, but not COX-1, is induced in the contracting smooth mucles of the ductus. In further studies, we have demonstrated that COX-1 or COX-2 selective inhibitors duplicate the results obtained with the COC knockout mice.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Intramural Research (Z01)
Project #
1Z01ES021179-10
Application #
6681841
Study Section
(LECM)
Project Start
Project End
Budget Start
Budget End
Support Year
10
Fiscal Year
2002
Total Cost
Indirect Cost

  Institution

Name
U.S. National Inst of Environ Hlth Scis
Department
Type
DUNS #
City
State
Country
United States
Zip Code

  Publications

Aid, Saba; Langenbach, Robert; Bosetti, Francesca (2008) Neuroinflammatory response to lipopolysaccharide is exacerbated in mice genetically deficient in cyclooxygenase-2. J Neuroinflammation 5:17
Choi, Sang-Ho; Langenbach, Robert; Bosetti, Francesca (2008) Genetic deletion or pharmacological inhibition of cyclooxygenase-1 attenuate lipopolysaccharide-induced inflammatory response and brain injury. FASEB J 22:1491-501
Narasimha, Ajay; Watanabe, Junji; Lin, James A et al. (2007) A novel anti-atherogenic role for COX-2--potential mechanism for the cardiovascular side effects of COX-2 inhibitors. Prostaglandins Other Lipid Mediat 84:24-33
Gitlin, Jonathan M; Trivedi, Darshini B; Langenbach, Robert et al. (2007) Genetic deficiency of cyclooxygenase-2 attenuates abdominal aortic aneurysm formation in mice. Cardiovasc Res 73:227-36
Carey, Michelle A; Bradbury, J Alyce; Seubert, John M et al. (2005) Contrasting effects of cyclooxygenase-1 (COX-1) and COX-2 deficiency on the host response to influenza A viral infection. J Immunol 175:6878-84
Rao, Jagadeesh S; Langenbach, Robert; Bosetti, Francesca (2005) Down-regulation of brain nuclear factor-kappa B pathway in the cyclooxygenase-2 knockout mouse. Brain Res Mol Brain Res 139:217-24
Kawada, Noritaka; Solis, Glenn; Ivey, Nathan et al. (2005) Cyclooxygenase-1-deficient mice have high sleep-to-wake blood pressure ratios and renal vasoconstriction. Hypertension 45:1131-8
Wang, Tongguang; Pei, Zhong; Zhang, Wei et al. (2005) MPP+-induced COX-2 activation and subsequent dopaminergic neurodegeneration. FASEB J 19:1134-6
Steiner, Alexandre A; Rudaya, Alla Y; Robbins, Jared R et al. (2005) Expanding the febrigenic role of cyclooxygenase-2 to the previously overlooked responses. Am J Physiol Regul Integr Comp Physiol 289:R1253-7
Salvatore, Michael F; Fisher, Brent; Surgener, Stewart P et al. (2005) Neurochemical investigations of dopamine neuronal systems in iron-regulatory protein 2 (IRP-2) knockout mice. Brain Res Mol Brain Res 139:341-7

Showing the most recent 10 out of 19 publications