Methods To understand the complexity of intracellular signalling pathway perturbation in TRAPS, a prototypic mutant TNFR1 (C33Y), or wild-type TNFR1 (WT), were expressed at near physiological levels in an SK-Hep-1 cell model system. TNFR1-associated signalling pathway intermediates were examined under a range of conditions, employing reverse-phase protein microarray. Peripheral blood mononuclea...

We investigated the effect of functional point mutations (Q730E) endoplasmic reticulum aminopeptidase 1 (ERAP1) on proliferation, apoptosis and cytokine secretion HaCaT cells. The ERAP1 ERAP1-Q730E were overexpressed in expression TNFR1 TNFR2 cells was detected by immunofluorescence. proliferation CCK-8. Cell cycle analyzed flow cytometry. IL-1β, TNF-α IL-6 ELISA. IKKs caspase-8 Western blot. o...

Activated tumor necrosis factor alpha (TNF-a) receptor 1 (TNFR1) recruits TNFR1-associated death domain protein (TRADD), which in turn triggers two opposite signaling pathways leading to caspase activation for apoptosis induction and NF-kB activation for antiapoptosis gene upregulation. Here we show that Stat1 is involved in the TNFR1-TRADD signaling complex, as determined by employing a novel ...

OBJECTIVE Mechanisms by which tumor necrosis factor-alpha (TNF) contributes to atherosclerosis remain largely obscure. We therefore sought to determine the role of the arterial wall TNF receptor-1 (TNFR1) in atherogenesis. METHODS AND RESULTS Carotid artery-to-carotid artery interposition grafting was performed with tnfr1-/- and congenic (C57Bl/6) wild-type (WT) mice as graft donors, and cong...

BACKGROUND Continuous angiotensin-II infusion induced the uptake of monocytic fibroblast precursors that initiated the development of cardiac fibrosis; these cells and concurrent fibrosis were absent in mice lacking tumor necrosis factor receptor 1 (TNFR1). We now investigated their cellular origin and temporal uptake and the involvement of TNFR1 in monocyte-to-fibroblast differentiation. MET...

In Chagas disease, understanding how the immune response controls parasite growth but also leads to heart damage may provide insight into the design of new therapeutic strategies. Tumor necrosis factor-alpha (TNF-alpha) is important for resistance to acute Trypanosoma cruzi infection; however, in patients suffering from chronic T. cruzi infection, plasma TNF-alpha levels correlate with cardiomy...

Guo, Guangjie, Jeremiah Morrissey, Ruth McCracken, Timothy Tolley, and Saulo Klahr. Role of TNFR1 and TNFR2 receptors in tubulointerstitial fibrosis of obstructive nephropathy. Am. J. Physiol. 277 (Renal Physiol. 46): F766–F772, 1999.—Unilateral ureteral obstruction (UUO) results in tubulointerstitial fibrosis of the obstructed kidney. In this study, we report the contribution of tumor necrosis...

Primary Sjögren's syndrome is an autoimmune disease affecting the function of exocrine glands. Tumor necrosis factor receptor-1 (TNFR1) is involved in apoptosis through extrinsic pathway initiation. The level of soluble TNFR1 is reported increased in rheumatoid arthritis, systemic lupus erythematosus, and primary Sjögren's syndrome patients. The TNFR1 gene contains a polymorphism that replaced ...

BACKGROUND Both total astragalus saponins (AST) and it's main component astragaloside IV (ASIV) have been used in China as cardiovascular protective medicines. However, the anti-inflammatory activities that are beneficial for cardiovascular health have never been compared directly and the molecular mechanisms remain unresolved. This study was conducted to compare the inhibitory effects of these...

Epidermal growth factor (EGF) and tumor necrosis factor-α (TNF-α) signaling are critical for effective proliferative and apoptotic actions; however, little is known about the codependency of these signaling pathways in the intestinal epithelium. Because total parenteral nutrition (TPN) is associated with loss of intestinal epithelial cell (IEC) proliferation and increased apoptosis, we utilized...