Introduction TNF receptor associated periodic syndrome (TRAPS) is an autosomal dominant disease caused by gain-of-function mutations in the TNF superfamily receptor 1A (TNFRSF1A) gene encoding 55 kDa TNF receptor type I (TNFR1). TRAPS is characterized by episodes of fever accompanied by severe abdominal pain, arthralgia, myalgia, rash, chest pain, enlarged glands and red, swollen eyes. Duration...

Ulcerative colitis is chronic and recurrent disease of the gastrointestinal tract with uncertain etiology and incomplete treatment options. N-methyl-d-aspartate (NMDA) receptor suppression has shown anti-inflammatory effects in vitro and in vivo. The aim of present study was to evaluate the role of dizocilpine (MK-801), a noncompetitive NMDA receptor antagonist, on TNBS (trinitrobenzene sulfoni...

Bone remodeling involves the resorption of bone by osteoclasts and the synthesis of bone matrix by osteoblasts. Receptor activator of NF-kappa B ligand (RANKL, also known as ODF and OPGL), a member of the tumor necrosis factor (TNF) family, triggers osteoclastogenesis by forming a complex with its receptor, RANK. We have determined the crystal structure of the extracellular domain of mouse RANK...

Our recent study detected the expression of a tissue renin–angiotensin system (tRAS) in human intervertebral discs (IVDs). The present sought to investigate impact angiotensin II receptor type 1 (AGTR1) antagonist losartan on nucleus pulposus (NP) cell inflammation and degeneration induced by tumor necrosis factor-α (TNF-α). Human NP cells (4 donors; Pfirrmann grade 2–3; 30–37-years–old; male) ...

In order to define the receptor binding site and the structure-functional relationship of tumor necrosis factor (TNF), single amino acid substitutions were made by site-directed mutagenesis at selected residues of human tumor necrosis factor, using a phagemid mutagenesis/expression vector. The recombinant TNF mutants were compared to the wild type TNF in assays using crude bacterial lysates, fo...

The receptors and ligands in this superfamily have unique structural attributes that couple them directly to signaling pathways for cell proliferation, survival, and differentiation. Thus, they have assumed prominent roles in the generation of tissues and transient microen-capabilities are crucial in coordinating the proliferation and protective functions of pathogen-reactive cells. Here, we re...

Tumor necrosis factor alpha (TNF-alpha) and TNF-beta are key mediators in bacterial inflammation. We therefore examined the role of TNF-alpha and its two receptors in murine pneumococcal central nervous system infection. TNF-alpha knockout mice and age- and sex-matched controls and TNF receptor (p55 and p75)-deficient mice and heterozygous littermates were infected intracerebrally with a Strept...

Circulating factors, such as agonistic autoantibodies to the angiotensin II type 1 (AT1) receptor (AT1-AAs), and inflammatory cytokines, including tumor necrosis factor alpha (TNF-alpha), are suggested to be important links between placental ischemia and hypertension in preeclamptic women. The purpose of this study was to determine the role of placental ischemia and TNF-alpha in stimulating the...

Chronic obstructive pulmonary disease (COPD) is characterised by a local pulmonary inflammatory response to respiratory pollutants and by systemic inflammation. Tumour necrosis factor (TNF)-alpha has been implicated in systemic effects of COPD and operates by binding the p55 (R1) and p75 (R2) TNF-alpha receptors. To investigate the contribution of each TNF-alpha receptor in the pathogenesis of ...