title: Effect of enhanced prostacyclin synthesis by adenovirus-mediated transfer on lipopolysaccharide stimulation in neuron-glia cultures.
abstract: Prostacyclin (PGI2) is known as a short-lived, potent vasodilator and platelet anti-aggregatory eicosanoid. This work attempts to selectively augment PGI2 synthesis in neuron-glia cultures by adenoviral (Ad) gene transfer of PGI synthase (PGIS) or bicistronic cyclooxygenase 1 (COX-1)/PGIS and examines whether PGI2 confers protection against lipopolysaccharide (LPS) stimulation. Cultures released low levels of eicosanoids. Upon Ad-PGIS or Ad-COX-1/PGIS infection, cultures selectively increased prostacyclin release. Both PGIS- and COX-1/PGIS-overexpressed cultures contained fewer microglial numbers. Further, they significantly attenuated LPS-induced iNOS expression and lactate, nitric oxide, and TNF-alpha production. Taken together, enhanced prostacyclin synthesis in neuron-glial cultures reduced microglia number and suppressed LPS stimulation.
authors.affiliation: Neural Regeneration Laboratory, Department of Neurosurgery, Neurological Institute, Taipei Veterans General Hospital, Shih-pai Road, Sec. 2, Taipei, Taiwan 11217.
authors.forename: May-Jywan
authors.initials: MJ
authors.lastname: Tsai
authors.forename: Song-Kun
authors.initials: SK
authors.lastname: Shyue
authors.forename: Ching-Feng
authors.initials: CF
authors.lastname: Weng
authors.forename: Ying
authors.initials: Y
authors.lastname: Chung
authors.forename: Dann-Ying
authors.initials: DY
authors.lastname: Liou
authors.forename: Chi-Ting
authors.initials: CT
authors.lastname: Huang
authors.forename: Huai-Sheng
authors.initials: HS
authors.lastname: Kuo
authors.forename: Meng-Jen
authors.initials: MJ
authors.lastname: Lee
authors.forename: Pei-Teh
authors.initials: PT
authors.lastname: Chang
authors.forename: Ming-Chao
authors.initials: MC
authors.lastname: Huang
authors.forename: Wen-Cheng
authors.initials: WC
authors.lastname: Huang
authors.forename: K D
authors.initials: KD
authors.lastname: Liou
authors.forename: Henrich
authors.initials: H
authors.lastname: Cheng
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D002478:Cells, Cultured; D018920:Coculture Techniques; D051545:Cyclooxygenase 1 / Q000235:genetics / Q000378:metabolism; D011464:Epoprostenol / Q000096:biosynthesis*; D005786:Gene Expression Regulation; D008070:Lipopolysaccharides / Q000494:pharmacology*; D009457:Neuroglia / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D009569:Nitric Oxide / Q000096:biosynthesis; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D008070:Lipopolysaccharides; D009569:Nitric Oxide; D011464:Epoprostenol; D051545:Cyclooxygenase 1; D011451:Prostaglandin-Endoperoxide Synthases