A novel lipopolysaccharide-response element contributes to induction of nitric oxide synthase

Abstract

The gene encoding the high output isoform of nitric oxide synthase represents a large class of alarm and defense genes transcriptionally induced in response to bacterial lipopolysaccharide (LPS). The promoters of most of these genes contain at least two LPS-response elements, one of which commonly binds transcription factors of the NF-κB/Rel family. Here a novel LPS- response element is identified in the inducible nitric oxide synthase promoter, termed LRE(AA), which contains critical adenosine residues lying 19-20 base pairs downstream of the proximal NF-κB binding element (NFκBd). Both NFκBd and LRE(AA) are required for LPS-induced promoter activity. A protein partially recognized by antibody against transcription factor Oct-1 binds to the LRE(AA) element constitutively in untreated macrophages while contributing to a DNA-protein complex that includes NF-κB p50 in macrophages treated with LPS. NF-κB p50 and the LRE(AA)-binding proteins may together recruit an LPS-triggered transactivator of transcription.