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Effect of Enhanced Prostacyclin Synthesis by Adenovirus‐Mediated Transfer on Lipopolysaccharide Stimulation in Neuron‐Glia Cultures
Author(s) -
TSAI MAYJYWAN,
SHYUE SONGKUN,
WENG CHINGFENG,
CHUNG YING,
LIOU DANNYING,
HUANG CHITING,
KUO HUAISHENG,
LEE MENGJEN,
CHANG PEITEH,
HUANG MINGCHAO,
HUANG WENCHENG,
LIOU K D,
CHENG HENRICH
Publication year - 2005
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1196/annals.1338.031
Subject(s) - prostacyclin , stimulation , microglia , nitric oxide , lipopolysaccharide , nitric oxide synthase , neuron , chemistry , cyclooxygenase , pharmacology , biology , inflammation , immunology , biochemistry , endocrinology , enzyme , neuroscience
A bstract : Prostacyclin (PGI 2 ) is known as a short‐lived, potent vasodilator and platelet anti‐aggregatory eicosanoid. This work attempts to selectively augment PGI 2 synthesis in neuron‐glia cultures by adenoviral (Ad) gene transfer of PGI synthase (PGIS) or bicistronic cyclooxygenase 1 (COX‐1)/PGIS and examines whether PGI 2 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‐α production. Taken together, enhanced prostacyclin synthesis in neuron‐glial cultures reduced microglia number and suppressed LPS stimulation.