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Volume 272, Number 23, Issue of June 6, 1997 pp. 14867-14872
©1997 by The American Society for Biochemistry and Molecular Biology, Inc.

A Novel Lipopolysaccharide-response Element Contributes to Induction of Nitric Oxide Synthase

(Received for publication, January 24, 1997, and in revised form, March 21, 1997)

From the Beatrice and Samuel A. Seaver Laboratory, Department of Medicine, Cornell University Medical College, New York, New York 10021

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-B/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-B binding element (NFBd). Both NFBd 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-B p50 in macrophages treated with LPS. NF-B p50 and the LRE_AA-binding proteins may together recruit an LPS-triggered transactivator of transcription.

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