Transcriptional regulation of the human iNOS gene in vascular-smooth-muscle cells and macrophages: evidence for tissue specificity.

Abstract:

:We have cloned the 5' upstream -1034 to +88 fragment of the human inducible nitric oxide synthase (hiNOS) gene and demonstrate its competence to promote luciferase gene transcription in vascular-smooth-muscle (VSM) cells and macrophages. Sequential 5' end-deletions localized positive regulatory elements of hiNOS transcription in VSM A7r5 cells downstream of nucleotide -205 and demonstrated the functional importance of the resident NF-kappaB site (nucleotides -115 to -106). The hiNOS promoter/enhancer was induced strongly by LPS and IFN-gamma, and modestly by IL-1beta in RAW 264.7 cells, but not in VSM cells. Truncation of the NF-kappaB site markedly diminished, but did not eliminate, LPS-inducibility. Sodium salicylate and ibuprofen down-regulated the basal transcriptional activity of the hiNOS promoter/enhancer in VSM but not in RAW 264.7 cells. These results indicate that the transcriptional regulation of the hiNOS gene features considerable complexity and tissue specificity.

authors

Kolyada AY,Savikovsky N,Madias NE

doi

10.1006/bbrc.1996.0449

subject

Has Abstract

pub_date

1996-03-27 00:00:00

pages

600-5

issue

3

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(96)90449-0

journal_volume

220

pub_type

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