The cytoplasmic C-terminus of Epstein-Barr virus (EBV) latent infection membrane protein 1 (LMP1) is essential for B lymphocyte growth transformation and is now shown to interact with a novel human protein (LMP1-associated protein 1 [LAP1]). LAP1 is homologous to a murine protein, tumor necrosis factor receptor-associated factor 2 (TRAF2), implicated in growth signaling from the p80 TNFR. A sec...

Signalling by the tumour necrosis factor receptors (TNFR) is thought to be mediated by the binding of the trimeric ligand TNF to three monomeric subunits of the receptor. This ligand induced trimerisation model of TNFR signalling is mainly supported by crystallographic data of the p60 TNFR-1 and TNFbeta complex in which the trimeric ligand interdigitates between the individual receptor chains a...

Expression of heat shock proteins (HSP) is an adaptive response to cellular stress. Stress induces tumor necrosis factor (TNF)-alpha production. In turn, TNF-alpha induces HSP70 expression. However, osmotic stress or ultraviolet radiation activates TNF-alpha receptor I (TNFR-I) in the absence of TNF-alpha. We postulated that TNF-alpha receptors are involved in the induction of HSP70 by cellular...

BACKGROUND The aim of the current study was to investigate the role of p55 TNF Receptor (p55 TNFR), the main signaling receptor for the pro-inflammatory cytokine tumor necrosis factor (TNF), in the development of two vascular disorders: atherosclerosis and angiotensin (Ang) II-induced abdominal aortic aneurysms (AAA). METHODOLOGY/PRINCIPAL FINDINGS p55 TNFR deficient mice were crossed to an L...

The role of TNFalpha in regulating apoptotic signaling was investigated during subacute, low-dose (5.0 mg/kg) dimethylnitrosamine (DMN)-induced hepatotoxicity. In TNFalpha receptor (TNFR) intact (wild-type, WT) mice following 4 and 7 DMN exposures, hepatic transcripts for TNFalpha and TNFR-1 were elevated as compared to vehicle controls. DMN hepatotoxicity in WT and TNFR-1/TNFR-2 double knockou...

RATIONALE Increasing evidence suggests that tumor necrosis factor (TNF)-alpha plays a key role in pulmonary injury caused by environmental ozone (O(3)) in animal models and human subjects. We previously determined that mice genetically deficient in TNF response are protected from lung inflammation and epithelial injury after O(3) exposure. OBJECTIVES The present study was designed to determin...

We hypothesized that tumor necrosis factor (TNF)-alpha signaling is essential to inflammation and host defense during Escherichia coli pneumonia. We tested this hypothesis by instilling E. coli into the lungs of wild-type (WT) mice and gene-targeted mice that lack both p55 and p75 receptors for TNF-alpha. The emigration of neutrophils 6 h after instillation of E. coli was not decreased, but rat...

Arachidonic acid (AA) regulates the function of many cell types, including neutrophils. Although much emphasis has been placed on agonist-induced down-regulation of TNFR, our data show that AA caused a rapid (10-20 min) and dose-dependent (0.5-30 micro M) increase in the surface expression of both classes of TNFR (TNFR1 and TNFR2) on human neutrophils. This increased TNFR expression correlated ...

Tumor necrosis factor (TNF)-alpha acts directly on adipocytes to increase production of the lipostatic factor, leptin. However, which TNF receptor (TNFR) mediates this response is not known. To answer this question, leptin was measured in plasma of wild-type (WT), p55, and p75 TNFR knockout (KO) mice injected intraperitoneally with murine TNF-alpha and in supernatants from cultured WT, p55, and...

Tumor necrosis factor- (TNF-) α is a proinflammatory cytokine involved in the development and maintenance of inflammatory and neuropathic pain. Its effects are mediated by two receptors, TNF receptor-1 (TNFR-1) and TNF receptor-2 (TNFR-2). These receptors play a crucial role in the sensitization of voltage-gated sodium channels (VGSCs), a key mechanism in the pathogenesis of chronic pain. Using...