TNF has been implicated in the pathogenesis of type 1 diabetes. When administered early in life, TNF accelerates and increases diabetes in NOD mice. However, when administered late, TNF decreases diabetes incidence and delays onset. TNFR1-deficient NOD mice were fully protected from diabetes and only showed mild peri-insulitis. To further dissect how TNFR1 deficiency affects type 1 diabetes, th...

The Epstein-Barr virus latent membrane protein 1 (LMP1) binds tumor necrosis factor receptor (TNFR)-associated factors (TRAFs) and the TNFR-associated death domain protein (TRADD). Moreover, it induces NF-kappaB and the c-Jun N-terminal kinase 1 (JNK1) pathway. Thus, LMP1 appears to mimick the molecular functions of TNFR1. However, TNFR1 elicits a wide range of cellular responses including apop...

Primary nociceptors relay painful touch information from the periphery to the spinal cord. Although it is established that signals generated by receptor tyrosine kinases TrkA and Ret coordinate the development of distinct nociceptive circuits, mechanisms modulating TrkA or Ret pathways in developing nociceptors are unknown. We have identified tumor necrosis factor (TNF) receptor 1 (TNFR1) as a ...

Neuroinvasion and subsequent destruction of the central nervous system by prions are typically preceded by a colonization phase in lymphoid organs. An important compartment harboring prions in lymphoid tissue is the follicular dendritic cell (FDC), which requires both tumor necrosis factor receptor 1 (TNFR1) and lymphotoxin β receptor (LTβR) signaling for maintenance. However, prions are still ...

BACKGROUND Selective inhibition of TNFR1 signaling holds the potential to greatly reduce the pro-inflammatory activity of TNF, while leaving TNFR2 untouched, thus allowing for cell survival and tissue homeostasis. ATROSAB is a humanized antagonistic anti-TNFR1 antibody developed for the treatment of inflammatory diseases. METHODOLOGY/PRINCIPAL FINDINGS The epitope of ATROSAB resides in the N-...

To determine the roles of the type 1 tumor necrosis factor (TNF) receptor (TNFR1) in lung inflammation and antibacterial defense, we exposed transgenic mice lacking TNFR1 [TNFR1(-/-)] and wild-type control mice to aerosolized lipopolysaccharide or Pseudomonas aeruginosa. After LPS, bronchoalveolar lavage fluid (BALF) from TNFR1(-/-) mice contained fewer neutrophils and less macrophage inflammat...

The 55-kDa, type I tumor necrosis factor receptor (TNFR1) can be released to the extracellular space by two mechanisms, the proteolytic cleavage and shedding of soluble receptor ectodomains and the release of full-length receptors within exosome-like vesicles. We have shown that the brefeldin A-inhibited guanine nucleotide-exchange protein BIG2 associates with TNFR1 and selectively modulates th...

Introduction: Recent studies have shown that intermittent normobaric hyperoxia (HO) protects the rat brain from ischemia reperfusion injury. However, the exact mechanism of this kind of protection in vivo is not known. In this study, the effect of HO on expression of TNFR1 and TNFR2 in a stroke model was investigated. Methods: In this experimental study, rats were divided into 4 groups: no...

One strategy adopted by vaccinia virus (VV) to evade the host immune system is to encode homologs of TNF receptors (TNFRs) that block TNF-α function. The response to VV skin infection under conditions of TNF-α deficiency, however, has not been reported. We found that TNFR1-/- mice developed larger primary lesions, numerous satellite lesions, and higher skin virus levels after VV scarification. ...