Expression of a constitutively active form of phosphatidylinositol 3-kinase inhibits the induction of nitric oxide synthase in human astrocytes

The present study underlines the importance of phosphatidylinositol 3-kinas e (PI 3-kinase) in attenuating the induction of nitric oxide synthase (iNOS ) in human astrocytes. Proinflammatory cytokines induced the production of nitric oxide ((NO) and the Expression of iNOS in human U373MG astrocytoma c ells and primary astrocytes. Expression of a catalytically active p110 subu nit (p110*) of PI 3-kinase but not that of a kinase-deficient mutant of p11 0 (p110-kd) induced an increase in PI 3-kinase activity and inhibited cytok ine-induced production of NO and expression of iNOS. However, expression of p110* had no effect on the activation of NF-kB, suggesting that p110* inhi bits the expression of iNOS without inhibiting the activation of NF-kB, (C) 2000 Federation of European Biochemical Societies.