Biologic tumor necrosis factor inhibitors (TNFIs) include TNF decoy receptors (TNFRs). TNFα plays a pathologic role in both acute and chronic brain disease. However, biologic TNFIs cannot be developed as brain therapeutics because these large molecule drugs do not cross the blood-brain barrier (BBB). To enable penetration of the brain via receptor-mediated transport, the human TNFR type II was ...

Tumor necrosis factor (TNF) receptor-associated factors (TRAFs) were identified as signal transducers for the tumor necrosis factor receptor (TNFR) superfamily. In this study, we cloned and characterized two genes that encode chicken TNFR-II and TRAF5. The initial cDNA fragments were obtained by suppressive subtractive hybridization (SSH) of chicken spleen cells with or without lipopolysacchari...

UNLABELLED The purpose of this study was to determine whether tumor necrosis factor (TNF) contributes to airway hyperresponsiveness (AHR) and migration of polymorphonuclear leukocytes (PMN) into the airways following exposure to ozone (O(3)). Wild-type mice, TNF p55 or p75 receptor knockout mice (p55 TNFR -/- and p75 TNFR -/-), as well as double receptor knockout mice (p55/p75 TNFR -/-), were e...

The effector function of CD8 T cells is mediated via cell-mediated cytotoxicity and production of cytokines like gamma interferon (IFN-gamma) and tumor necrosis factor alpha (TNF-alpha). While the roles of perforin-dependent cytotoxicity, IFN-gamma, and TNF-alpha in controlling acute viral infections are well studied, their relative importance in defense against chronic viral infections is not ...

Tumor necrosis factor alpha (TNF-alpha) is a proinflammatory cytokine. Its pleiotropic biological properties are signaled through two distinct cell surface receptors: the TNF receptor type I (TNFR-I) and the TNF receptor type II. Neither of the two receptors possesses tyrosine kinase activity. A large majority of TNF-alpha-dependent activities can be mediated by TNFR-I. Recently, c-Raf-1 kinase...

Human monocytic leukemia U937 cells readily undergo apoptosis when cells are treated with various stimuli including antitumor agents, tumor necrosis factor (TNF)-alpha and anti-Fas antibody. However, the signal transduction mechanism resulting in apoptosis is unclear. To study the mechanism of apoptosis, we isolated and characterized a mutant, UK110, from U937 cells, which was resistant to TNF-...

Two tumor necrosis factor receptors (TNFRs) with molecular weights of 55 kD (TNFR-p55) and 75 kD (TNFR-p75) have recently been identified and cloned. In previous studies, TNFR-p55 has been shown to exclusively mediate bidirectional effects of TNF-alpha on committed bone marrow granulocyte-macrophage progenitor cells, whereas both TNFR-p55 and TNFR-p75 can mediate inhibition of primitive progeni...

OBJECTIVE To evaluate the efficacy and safety of tumor necrosis factor (TNF) inhibition with the p55 TNF receptor fusion protein (TNFr-Ig) for severe sight-threatening noninfectious posterior segment intraocular inflammation. METHODS Seventeen patients with refractory noninfectious posterior segment intraocular inflammation received TNFr-Ig by intravenous infusion in this nonrandomized, open-...

INTRODUCTION The tumor necrosis factor receptor (TNFR) family consists of a number of type I transmembrane glycoproteins characterized by homologous cysteine-rich domains in their extracellular region. The intracellular parts of these proteins vary in size and structure, corresponding to the wide array of functions of TNFR proteins, ranging from regulation of cell activation and differentiation...

Blood-stage Plasmodium chabaudi AS infection was controlled by 4 weeks in mice with deletion of tumor necrosis factor p55 and p75 receptors (TNFR-knockout [KO]) and control wild-type (WT) mice, although female TNFR-KO mice showed slightly but significantly higher parasitemia immediately following the peak. Serum interleukin 12 (IL-12) p70 and gamma interferon (IFN-gamma) levels were similar but...