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The effect of a peptide homologous to the biologically active fragment of β amyloid 25–35 (β 25–35) was studied on interleukin 6 (IL-6) and tumour necrosis factor (TNF-α) secretion induced by lipopolysaccharide (LPS) in primary rat astrocytes and microglia. Twenty-four hour exposure to LPS (50 ng/ml) induced IL-6 and TNF-α both in astrocytes and in microglial cells, while the effect of β 25–35 (50...
In allergic disorders, the role of tumor necrosis factors (TNF) is not well established. We investigated the role of TNF in allergic peritonitis induced by ovalbumin (OVA) challenge in double TNF (TNF-α -/- /lymphotoxin-α -/- ) knock out (TNF-KO) mice. In the peritoneal lavage of TNF-KO mice, mast cell number and histamine level (radioenzymatic assay) were similar...
The G to A single nucleotide polymorphisms (SNPs), at position -376, -308 and -238 in the promoter of the tumor necrosis factor alpha (TNF) gene, have been independently correlated with numerous diseases. Alleles TNF -376A and TNF -238A are normally found throughout the world with very low frequencies. We investigated the frequency of these SNPs...
A role for pro-inflammatory cytokines in inflammation-related cancers has been suggested, but mechanisms are not defined. Here, we demonstrate that treatment of HeLa cells with TNFα increases chromosomal aberration. In contrast, IL-1β did not increase, but rather decreased chromosomal aberration. TNFα and IL-1β increased the production of H 2 O 2 to similar levels in cells, suggesting...
Systemic Lupus Erythematosus (SLE) is an autoimmune disease characterized by a wide variety of autoantibodies, some of which are pathogenic. In recent years it has become more evident that the polyclonal B cell activation in SLE is T-cell dependent. The stimulation of the autoantibody producing B cells is likely mediated by the TH2 subtype of T cells producing IL-4, IL-5, IL-6 and IL- 10, whereas...
The roles played by the non-covalent interactions have been investigated for a set of six TNF proteins and nine Interleukins. The stabilizing residues have been identified by a consensus approach using the concepts of available surface area, medium and long-range interactions and conservation of amino acid residues. The cation–π interactions have been computed based on a geometric approach such as...
Sepsis is a systemic inflammatory response syndrome resulting from an inappropriate innate immune response to infection. TNF and interleukin (IL)-6 are critically involved in this syndrome and although conclusive in vivo evidence is missing, innate immune cells are believed to be the principal producers of these cytokines. We investigated this assumption by performing bone marrow transplantations...
The tumor necrosis factor (TNF) family of cytokines and their receptors regulates many areas of metazoan biology. Specifically, this cytokine-receptor family plays crucial roles in regulating myriad aspects of immune development and functions. Disruption of ligand–receptor interaction or downstream signal transduction components in the TNF family often leads to pathological conditions. Historically,...
TL1A is a recently discovered TNF-like ligand. Because of the interests in the structural basis of the specificity of the bindings of the TNF ligands to the TNF receptors, we sought to crystallize the mature soluble form of human TL1A. To prepare recombinant human TL1A, the coding sequence for mature human soluble TL1A (aa72–aa251) was cloned into Escherichia coli expression vector pDEST14 and the...
Conserved molecular patterns of microbial pathogens, such as lipopolysaccharide (LPS) and cytosine-phosphate-guanine (CpG) DNA motifs are important signals for receptor-mediated activation of innate immune cells. It has been shown that the liver-specific transcription-blocking d-galactosamine (d-GalN) severely sensitizes to the lethal effects of LPS and CpG DNA. Lethality of LPS or CpG DNA in GalN-treated...
Stem cells have shown promise for the treatment of end organ ischemia. NFkB has been demonstrated to regulate growth factor secretion in human adult bone marrow stem cells (aBMSCs). We hypothesized that: (1) NFkB is an important mediator in aBMSC and neonatal BMSC (nBMSC) VEGF and IL-6 secretion; and (2) inhibition of NFkB will result in a decrease of VEGF and IL-6 in nBMSCs. BMSCs were plated and...
Obesity with insulin resistance and alcohol are the most frequent causes of steatohepatitis. This work investigates the contribution of bioactive TNF and Th1 type cytokines in a mouse model of steatohepatitis induced by FAT alone or FAT+EtOH and endotoxin. The extent of liver injury and cytokine activation induced by endotoxin in chronic FAT-fed mice, FAT+EtOH-fed mice, or mice fed standard chow were...
Elevated serum macrophage migration inhibitory factor (MIF) is associated with severe sepsis, but it is not clear whether bacteria stimulate synthesis of MIF by blood leukocytes directly or via induction of TNF. Here we assess production of MIF mRNA and protein by blood leukocytes from healthy human subjects (n=28) following exposure to bacteria commonly associated with sepsis (Escherichia coli and...
ADAM17 (a disintegrin and metalloprotease)-deficient murine fibroblasts stably transfected with proTNF cDNA release significant amounts of biologically active soluble TNF. The enzyme responsible for this activity is a membrane protein that hydrolyzes the peptide bond Ala 76 :Val 77 within proTNF. Its activity is inhibited by 1,10-phenantroline and GM6001, insusceptible to TIMP-2 (tissue...
Objective: To investigate differences in cytokine production between influenza A and B. Materials and methods: thirty one patients with influenza A and 16 with influenza B were enrolled in this study. We measured soluble tumor necrosis factor receptor (sTNFR) 1, interleukin (IL)-6, interferon (IFN)-γ and IL-4 concentrations in serum obtained from all patients during the acute and convalescence phases...
Tumor necrosis factor (TNF) and the members of the interferon (IFN) family are major inducible cytokines that function to counteract viral infections or cellular transformation. Recently, our lab has characterized a novel antiviral state which is induced in primary human fibroblasts by co-treatment with TNF plus IFNβ. Here, we demonstrate that this synergistic state is both antiviral and cytostatic...
The mTOR signaling pathway plays a very important role in the transmission of signals for initiation of mRNA translation and protein expression in mammalian cells. mTOR activates various downstream effectors to promote initiation of cap-dependent mRNA translation and mediate pro-mitogenic and pro-survival signals. Recent evidence has implicated effectors of this signaling cascade in mRNA translation...
Although there is evidence suggesting that statins may exert an endothelial protecting effect, recent in vitro data have shown that these compounds may induce endothelial cells (EC) apoptosis. We previously reported that the Fas-death receptor may induce apoptosis of the liver sinusoid endothelial cells (LSEC), and that TNF-α increases the susceptibility of these cells to suffer Fas-mediated apoptosis...
The heat shock (HS) response, a phylogenetically conserved ubiquitous response to stress, is generally characterized by the induced expression of heat shock protein (HSP) genes. Our earlier studies showed that the stress-activated transcription factor, heat shock factor-1 (HSF1), activated at febrile range or HS temperatures also modified expression of non-HSP genes including cytokine and chemokine...
The presence of low-grade chronic inflammation is a known feature of long standing diabetes type 1. The association between serum level of several markers of inflammation and severity of DM1 was proven. Serum concentrations of TNF were reported to be elevated in diabetic patients, especially those who developed diabetic complications. Lately, it has been also shown that TNF may impair the subset of...
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