Effect of enhanced prostacyclin synthesis by adenovirus-mediated transfer on lipopolysaccharide stimulation in neuron-glia cultures.
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.
Tsai
May-Jywan
MJ
Neural Regeneration Laboratory, Department of Neurosurgery, Neurological Institute, Taipei Veterans General Hospital, Shih-pai Road, Sec. 2, Taipei, Taiwan 11217.
Shyue
Song-Kun
SK
Weng
Ching-Feng
CF
Chung
Ying
Y
Liou
Dann-Ying
DY
Huang
Chi-Ting
CT
Kuo
Huai-Sheng
HS
Lee
Meng-Jen
MJ
Chang
Pei-Teh
PT
Huang
Ming-Chao
MC
Huang
Wen-Cheng
WC
Liou
K D
KD
Cheng
Henrich
H
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
D008070:Lipopolysaccharides; D009569:Nitric Oxide; D011464:Epoprostenol; D051545:Cyclooxygenase 1; D011451:Prostaglandin-Endoperoxide Synthases