title: Serum-dependent potentiation of lipopolysaccharide-induced nitric oxide production is mediated by the events after the transcription of inducible type of nitric oxide synthase.
abstract: The mechanism of serum-dependent potentiation of lipopolysaccharide (LPS)-induced nitric oxide (NO) production was studied by incubating mouse macrophage cell line, RAW 264.7, in the presence of fetal bovine serum (FBS). The addition of FBS definitely enhanced LPS-induced NO production through augmented expression of inducible type NO synthase (iNOS) mRNA and protein. However, nuclear run-on analysis demonstrated only marginal enhancement in the rate of LPS-induced iNOS gene transcription in the presence of FBS. Further, there was no significant difference in the luciferase reporter gene activity linked to the iNOS promoter-enhancer gene in response to LPS between the presence and absence of FBS. FBS-dependent enhancement did not appear to involve the initial step for triggering iNOS transcription in LPS-induced NO production. Rather, FBS was suggested to affect the accumulation and stabilization of iNOS mRNA leading to iNOS protein and NO production by some post-transcriptional regulatory mechanism.
authors.affiliation: Department of Microbiology, Molecular Genetics, and Immunology, University of Kansas Medical Center, Kansas City, KS 66160-7184, USA.
authors.forename: Yue H
authors.initials: YH
authors.lastname: Zhang
authors.forename: William J
authors.initials: WJ
authors.lastname: Murphy
authors.forename: Stephen W
authors.initials: SW
authors.lastname: Russell
authors.forename: David C
authors.initials: DC
authors.lastname: Morrison
authors.forename: Naoki
authors.initials: N
authors.lastname: Koide
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Yoshida
authors.forename: Takashi
authors.initials: T
authors.lastname: Yokochi
mesh_terms: D000818:Animals; D002417:Cattle; D002460:Cell Line; D005786:Gene Expression Regulation / Q000187:drug effects; D008070:Lipopolysaccharides / Q000494:pharmacology*; D051379:Mice; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000235:genetics* / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D044967:Serum / Q000502:physiology*; D015398:Signal Transduction; D014158:Transcription, Genetic / Q000187:drug effects*
chemical_list: D008070:Lipopolysaccharides; D012333:RNA, Messenger; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse