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Transforming Growth Factor β1 Regulates the Expression of Cyclooxygenase in Cultured Cortical Astrocytes and Neurons
Author(s) -
Luo Jia,
Lang Julie A.,
Miller Michael W.
Publication year - 1998
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1998.71020526.x
Subject(s) - astrocyte , cyclooxygenase , phospholipase a2 , arachidonic acid , prostaglandin e2 , transforming growth factor , neuroglia , biology , microbiology and biotechnology , endocrinology , medicine , prostaglandin , cytosol , microglia , chemistry , central nervous system , immunology , enzyme , biochemistry , inflammation
The hypothesis that transforming growth factor β1 (TGFβ1) regulates the synthesis of prostaglandins by CNS tissue was tested by using purified cultures of cortical astrocytes or neurons that were obtained from rat pups on postnatal day 4 or 5 or fetuses on gestational day 16, respectively. The cells were exposed to TGFβ1 for 2 days. The synthesis of prostaglandins depends upon the production and conversion of arachidonic acid, steps that are catalyzed by phospholipase A 2 (PLA 2 ) and cyclooxygenase (COX), respectively. Prostaglandin E 2 (PGE 2 ) concentration was determined by radioimmunoassay. The expression of cytosolic PLA 2 and COX (the constitutive COX1 and the inducible COX2) was assessed by using immunohistochemical and quantitative immunoblotting procedures. Astrocytes produced much more PGE 2 than neurons, suggesting that glial cells are an important source of PGE 2 in the CNS. TGFβ1 increased the production of PGE 2 by astrocytes and neurons in a concentration‐dependent manner. Furthermore, TGFβ1 enhanced COX activity; the inhibitor indomethacin completely blocked TGFβ1‐mediated PGE 2 synthesis. Cultured astrocytes and neurons expressed the three enzymes: cytosolic PLA 2 , COX1, and COX2. Cytosolic PLA 2 expression was unaffected by TGFβ1 treatment. In contrast, COX expression was altered by TGFβ1 treatment in a concentration‐dependent fashion. COX1 was increased by TGFβ1, but only in astrocytes. TGFβ1 increased COX2 expression in astrocytes and neurons. Thus, TGFβ1‐induced increases in PGE 2 concentration are regulated by COX. This study suggests that TGFβ1 is an important regulator of immune and inflammatory processes in the CNS.