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B Nuclear Localization Is Efficacious in Models of Inflammatory Disease
Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, NJ 08543
The transcription factor NF-
B regulates many genes involved in
proinflammatory and immune responses. The transport of NF-B into the
nucleus is essential for its biologic activity. We describe a novel,
potent, and selective NF-B inhibitor composed of a cell-permeable
peptide carrying two nuclear localization sequences (NLS). This peptide
blocks NF-B nuclear localization, resulting in inhibition of cell
surface protein expression, cytokine production, and T cell
proliferation. The peptide is efficacious in vivo in a mouse septic
shock model as well as a mouse model of inflammatory bowel disease,
demonstrating that NF-B nuclear import plays a role in these acute
inflammatory disease models.
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