Tumor necrosis factor alpha TNF

Other pro-inflammatory factors produced and secreted by these cell populations snch as interlenkins (IL) -1, -6, -12, and tumor necrosis factor alpha (TNF-a) are instrnmental in the resolution of bacterial clearance (Daley et al. 2005 Ishikawa and Miyazak 2005 Kudo et al. 2005 Man et al. 2007 Wang et al. 2005 Warner and Srinivasan 2004). 

Early research showed that Pb exposure could increase sensitivity to bacterially-derived endotoxins [63] as well as increase production of the pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-a) by macrophages [64-67], Studies in several species indicate that Pb boosts production of TNF-a both immediately following adult exposure and in later life following gestational exposure. Flohe and coworkers [67] reported that Pb-induced elevation in TNF-a production is sensitive to both protein kinase C signaling as well as protein production. Not only can the production of TNF-a be elevated following exposure to Pb, but also the expression of the receptor for TNF-a (TNF-R) is elevated [68], Therefore, the combined effect of elevated cytokine production by macrophages as well as increased receptor expression would be expected to contribute to problematic inflammatory responses. 

Recently, the possibility to use C60 as anti-inflammatory compound has been reported (Huang et al., 2008). Fullerene-xanthine hybrids have been studied to determine if nitric oxide (NO) and tumor necrosis factor-alpha (TNF-a) production in lipopolysaccharide (LPS)-activated macrophages can be inhibited by hybrid administration, finding positive results. The presence of xanthine moiety seems to be essential for the inhibition of LPS-induced TNF-a production, while the fullerene portion ameliorates the efficiency in LPS-induced NO production blockage, leading to a new promising class of potent anti-inflammatoiy agents. It is necessary to mention also the opposite results obtained by an amino acid fullerene derivative tested on human epidermal keratinocytes at concentration from 0.4 to 400 pg/mL. 

There is a great deal of evidence that AmB can exert a number of effects directly on cells of the immune system, and particularly on macrophages to increase nonspecific defense mechanisms against pathogens and cancer cells. These mechanisms include the production of nitric oxide (NO) (32) and tumor necrosis factor alpha (TNF-a) (33), which could contribute to the antifungal and antiparasitic activity of AmB. However, excess TNF-a production could also be responsible for some of the side effects associated with AmB treatment, such as fever and chills. 

Infliximab neutralizes the biological activity of tumor necrosis factor alpha (TNF ) by high-affinity binding to its soluble and transmembrane forms and inhibits TNF receptor binding. Infliximab does not neutralize TNF (lymphotoxin ), a related cytokine that uses the same receptors as TNF . 

Mauceri HJ, Hanna NN, Wayne JD, et al. Tumor necrosis factor alpha (TNF-alpha) gene therapy targeted by ionizing radiation selectively damages tumor vasculature. Cancer Res 1996 56 4311-4314. 

Buescher, E. S., and Williams-Koeppen, P. (1998). Soluble tumor necrosis factor-alpha (TNF-alpha) receptors in human colostrum and milk bind to TNF-alpha and neutralize TNF-alpha bioactivity. Pediatr. Res. 44, 37—42. 

Infliximab, anti tumor necrosis factor alpha TNF(alpha), chimeric human IgGl... 

Several benzothiadiazepines, as potent and selective TACE inhibitors, have been synthesized with variation in P1 and PI and evaluated versus porcine TACE, and the initial selectivity was assessed with counterscreens of MMP-1, MMP-2, and MMP-9. Several potent and selective inhibitors were discovered, 440 being the most active against porcine TACE. Most compounds were assessed in the human peripheral blood mononuclear cell (PBMC) assay and the human whole blood assay (WBA) to determine their ability to suppress tumor necrosis factor alpha (TNF-a). Compound 441 was found to be the most potent in the PBMC assay (IC50 = 0.35 pM), while 442 was the most active in the WBA (IC50 = 1.4 pM) <2003JME1811>. 

Several agents are now available that inhibit the action of tumor necrosis factor-alpha (TNF-a). TNF-a is a small protein (cytokine) that is released from cells involved in the inflammatory response. TNF-a seems to be a key chemical mediator that promotes inflammation and joint erosion in rheumatoid arthritis.83 Drugs that inhibit this chemical will therefore help delay the progression of this disease by decreasing TNF-a s destructive effects.70... 

FIGURE 16-2 T Schematic diagram illustrating the effects of tumor necrosis factor-alpha (TNF-a) inhibitors. Drugs such as etanercept, infliximab, and adalimumab attach directly to TNF-a, thereby preventing this destructive cytokine from reaching joint tissues. See text for more details. 

Finally, antibodies such as adalimumab (Humira) and infliximab (Remicade) have been developed that bind directly to tumor necrosis factor alpha (TNF-alpha), thereby preventing this cytokine from causing damage to joints and other tissues. These anti-TNF-alpha drugs are therefore helpful in autoimmune diseases such as rheumatoid arthritis their pharmacology is addressed in more detail in Chapter 16. 

Very little work has been reported on the role of oxidative stress in osteoblasts. However, osteoblasts can be induced to produce intracellular ROS (Cortizo et al., 2000 Liu et al., 1999), which can cause a decrease in alkalinephosphatase (ALP) activity that is partially inhibited by vitamin E and cause cell death (Cortizo et al., 2000 Liu et al., 1999). Treatment of rat osteosarcoma ROS 17/2.8 cells with tumor necrosis factor-alpha (TNF-a) suppressed bone sialoprotein (BSP) gene transcription through a tyrosine kinase-dependent pathway that generates ROS (Samoto et al., 2002). H202 modulated intracellular calcium (Ca2+) activity in osteoblasts by increasing Ca2+ release from the intracellular Ca2+ stores (Nam et al., 2002). 

Tumor necrosis factor alpha (TNF-alpha) 1995 D Factor 16 (IPCR 6,25 pg/ml ELISA 100 pg/ml) Sanna et al. [33]... 

Bruunsgaard H, Skinh0J P, Pedersen AN, Schroll M, Pedersen BK. Ageing, tumor necrosis factor-alpha (TNF-a) and atherosclerosis. Clin Exp Immunol. 2000, 121 255-260. 

Victor, F.C., Gottlieb, A.B., and Menter, A. 2003. Changing paradigms in dermatology Tumor necrosis factor alpha (TNF-alpha) blockade in psoriasis and psoriatic arthritis. Clin Dermatol 21 392-397. 

The LBP facilitates the binding of LPS or GNB to phagocytes (Tobias et al., 1988 Corriveau and Danner, 1993 Yu and Wright, 1996). The enhanced interaction between LPS and phagocytes causes a marked increase in cell activation. Addition of small amounts of LBP to cultured macrophages increases by 100-fold the ability of LPS to induce the production of tumor necrosis factor alpha (TNF-a), a potent... 

TNF-a Tumor necrosis factor alpha TNF ligand, TNFA, cachectin... 

Earlier studies have also shown that ricin induces oxidative stress in mice, resulting in increased urinary excretion of MDA and formaldehyde (FA) (Muldoon et al, 1994). Other toxicants have been shown to induce oxidative stress by macrophage activation with subsequent release of reactive oxygen species and tumor necrosis factor alpha (TNF-a). 

Chronic excessive nutrient intake leads to the deposition of fat, in not only its normal storage site, which is the adipose tissue, but also in liver and skeletal muscle. Nutrient excess also triggers an inflammatory response, with the release of inflammatory cytokines [tumor necrosis factor-alpha (TNF-a), interleukin-6 (IL-6), and CRP]. These inflammatory mediators, along with the intracellular accumulation of lipid metabolites, lead to impaired insulin receptor signaling and defective metabolism in skeletal muscle and liver (37, 38). Nutrient excess also damages cells by generating reactive oxygen species, which results... 

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