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

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-kappa B/Rel family. Here a novel LPS-response element is identified in the inducible nitric oxide synthase promoter, termed LREAA, which contains critical adenosine residues lying 19-20 base pairs downstream of the proximal NF-kappa B binding element (NF kappa Bd). Both NF kappa Bd and LREAA are required for LPS-induced promoter activity. A protein partially recognized by antibody against transcription factor Oct-1 binds to the LREAA element constitutively in untreated macrophages while contributing to a DNA-protein complex that includes NF-kappa B p50 in macrophages treated with LPS. NF-kappa B p50 and the LREAA-binding proteins may together recruit an LPS-triggered transactivator of transcription.