Bacterial lipopolysaccharide increases prostaglandin production by rat astrocytes via inducible cyclo-oxygenase: Evidence for the involvement of nuclear factor kappa B

This study was set to investigate the mechanisms through which bacterial li popolysaccharide (LPS) stimulates prostaglandin (PG) production in rat astr ocytes. Primary cultures of rat hypothalamic astrocytes were established. C ells were treated with LPS alone or LPS plus antagonists of various pathway s, and the subsequent changes in cyclo-oxygenase (COX) activity were monito red by measuring a COX end product, PGE2, released into the incubation medi um. It was found that (i) LPS produced a concentration-dependent increase i n PGE2 release from astrocytes. The potency of LPS was significantly increa sed by the addition of serum into the incubation medium; (ii) after 24 h of incubation, inducible COX (COX-2) accounts for most of the LPS-stimulated PG production, as the latter was markedly reduced by dexamethasone and the specific COX-2 inhibitor NS 398; and (iii) nuclear factor kappa B appears t o play a role in the activation of COX-2 induced by LPS, since certain inhi bitors of this transcription factor were able to antagonize, at least in pa rt, the effects of LPS on PGE2 release. (C) 1999 Academic Press.