Fujihara S M, Cleaveland J S, Grosmaire L S, Berry K K, Kennedy K A, Blake J J, Loy J, Rankin B M, Ledbetter J A, Nadler S G
Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, NJ 08543, USA.
J Immunol. 2000 Jul 15;165(2):1004-12. doi: 10.4049/jimmunol.165.2.1004.
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.
转录因子NF-κB调控许多参与促炎和免疫反应的基因。NF-κB转运至细胞核对其生物学活性至关重要。我们描述了一种新型、强效且具有选择性的NF-κB抑制剂，它由携带两个核定位序列（NLS）的细胞可渗透肽组成。这种肽可阻断NF-κB的核定位，从而抑制细胞表面蛋白表达、细胞因子产生及T细胞增殖。该肽在小鼠脓毒症休克模型以及炎症性肠病小鼠模型中体内有效，表明NF-κB的核输入在这些急性炎症疾病模型中发挥作用。
