Serum-dependent potentiation of lipopolysaccharide-induced nitric oxide production is mediated by the events after the transcription of inducible type of nitric oxide synthase.
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.
Zhang
Yue H
YH
Department of Microbiology, Molecular Genetics, and Immunology, University of Kansas Medical Center, Kansas City, KS 66160-7184, USA.
Murphy
William J
WJ
Russell
Stephen W
SW
Morrison
David C
DC
Koide
Naoki
N
Yoshida
Tomoaki
T
Yokochi
Takashi
T
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*
D008070:Lipopolysaccharides; D012333:RNA, Messenger; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse