A D-amino acid peptide inhibitor of NF-kappa B nuclear localization is efficacious in models of inflammatory disease.

Autor: Fujihara SM; Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, NJ 08543, USA., Cleaveland JS, Grosmaire LS, Berry KK, Kennedy KA, Blake JJ, Loy J, Rankin BM, Ledbetter JA, Nadler SG
Jazyk: angličtina
Zdroj: Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2000 Jul 15; Vol. 165 (2), pp. 1004-12.
DOI: 10.4049/jimmunol.165.2.1004
Abstrakt: The transcription factor NF-kappa B regulates many genes involved in proinflammatory and immune responses. The transport of NF-kappa B into the nucleus is essential for its biologic activity. We describe a novel, potent, and selective NF-kappa B inhibitor composed of a cell-permeable peptide carrying two nuclear localization sequences (NLS). This peptide blocks NF-kappa 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-kappa B nuclear import plays a role in these acute inflammatory disease models.
Databáze: MEDLINE