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.
Citations
Related Concepts
Related Feeds
CREs: Gene & Cell Therapy
Gene and cell therapy advances have shown promising outcomes for several diseases. The role of cis-regulatory elements (CREs) is crucial in the design of gene therapy vectors. Here is the latest research on CREs in gene and cell therapy.