Tumor necrosis factor-alpha , inhibition

Qin, L., Ding, Y., Pahud, D.R., Chang, E., Imperiale, M.J. and Bromberg, J.S. (1997) Promoter attenuation in gene therapy interferon-gamma and tumor necrosis factor-alpha inhibit transgene expression. Hum. Gene Then, 8, 2019-2029. 

Wispe JR, Clark JC, Warner BB et al (1990) Tumor necrosis factor-alpha inhibits expression of pulmonary surfactant protein. J Clin Invest 86(6) 1954-1960... 

TNF-a Tumor necrosis factor alpha Inhibits tumor cells mediates immune response against bacterial infection induces septic shock, autoimmune diseases, rheumatoid arthritis, inflammation, and diabetes... 

Rask-Madsen C, Dominguez H, Dilemann N, et al. Tumor necrosis factor-alpha inhibits insulin s stimulating effect on glucose uptake and endothelium-dependent vasodilation in humans. Circulation 2003 108 1815-1821. 

Vassallo R, Matteson E, Thomas CF Jr. Clinical response of rheumatoid arthritis-associated pulmonary fibrosis to tumor necrosis factor-alpha inhibition. Chest... 

Ahn SY, Cho CH, Park KG, Lee HI, Lee S, Park SK, Lee IK, Koh GY (2004) Tumor necrosis factor-alpha induces fractaUdne expression preferentially in arterial endothelial cells and mithramycin A suppresses TNF-alpha-induced fractaUdne expression. Am J Pathol 164 1663-1672 Alfano M, Schmidtmayerova H, Amelia CA, Pushkarsky T, Bukrinsky M (1999) The B-oligomer of pertussis toxin deactivates CC chemokine receptor 5 and blocks entry of M-tropic HIV-1 strains, [see comments]. J Exp Med 190 597-605 Ambrosini E, Alois F (2004) Chemokines and glial cells a complex network in the central nervous system. [Review] [239 refs]. Neurochem Res 29 1017-1038 Azuma Y, Ohura K (2002) Endomorphins 1 and 2 inhibit IL-10 and IL-12 production and innate immune functions, and potentiate NE-kappaB DNA binding in THP-1 differentiated to macrophagelike cells. Scand J Immunol 56 260-269... 

P16. van der Poll, T., Coyle, S. M., Barbosa, K., Braxton, C. C., and Lowry, S. F., Epinephrine inhibits tumor necrosis factor-alpha and potentiates interleukin-10 production during human en-dotoxemia. J. Clin. Invest. 97,713-719 (1996). 

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. 

Ohlsson, B.C., Englund, M.C., Karlsson, A.L., Knutsen, E., Erixon, C, Skribeck, H., Liu, Y., Bondjers, G., and Wiklund, O., 1996, Oxidized low density lipoprotein inhibits hpopolysaccharide-induced binding of nuclear factor-kappaB to DNA and the subsequent expression of tumor necrosis factor-alpha and interleukin-1 beta in macrophages, J. Clin. Invest. 98 78-89. 

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 . 

NT095 Higashimoto, Y., Y. Shimada, Y. Fuku-chi, et al. Inhibition of mouse alveolar macrophage production of tumor necrosis factor alpha by acute in vivo and in vitro exposure to tobacco smoke. NT105 Respiration 1992 59(2) 77—80. 

Mechanism of Action An immunomodulator whose exact mechanism is unknown. Has sedative, anti-inflammatory, and immunosuppressive activity, which may be due to selective inhibition of the production of tumor necrosis factor-alpha. Therapeutic Effect Improves muscle wasting in HIV patients reduces local and systemic effects of leprosy. 

McCormack DG, Clarke B, Barnes PJ (1989) Characterization of adenosine receptors in human pulmonary arteries. Am J Physiol 256(2) H41-H46 McWhinney CD, Dudley MW, Bowlin TL, Peet NP, Schook L, Bradshaw M, De M, Borcherding DR, Edwards CK 3rd (1996) Activation of adenosine A3 receptors on macrophages inhibits tumor necrosis factor-alpha. Eur J Pharmacol 310(2-3) 209-216 Mentzer RM Jr, Rubio R, Berne RM (1975) Release of adenosine by hypoxic canine lung tissue and its possible role in pulmonary circulation. Am J Physiol 229(6) 1625-1631 Meyerhof W, Mtiller-Brechlin R, Richter D (1991) Molecular cloning of a novel putative G-protein coupled receptor expressed during rat spermiogenesis. FEBS Lett 284(2) 155-160... 

Yu H, Pan C, Zhao S, Wang Z, Zhang H, Wu W. 2008. Resveratrol inhibits tumor necrosis factor-alpha-mediated matrix metalloproteinase-9 expression and invasion of human hepatocellular carcinoma cells. Biomed Pharmacother. 62 366-372. 

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... 

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). 

Spyridopoulos, I., Brogi, E., Kearney, M., Sullivan, A.B., Cetrulo, C., Isner, J.M., and Losardo, D.W. 1997. Vascular endothelial growth factor inhibits endothelial cell apoptosis induced by tumor necrosis factor alpha balance between growth and death signals. J. Mol. Cell. Cardiol. 29 1321-1330. 

Ponnappa BC, Israel Y, Aini M, Zhou F, Russ R, Cao QN, Hu Y, Rubin R. Inhibition of tumor necrosis factor alpha secretion and prevention of liver injury in ethanol-fed rats by antisense oligonucleotides. Biochem Pharmacol 2005 69(4) 569-77. 

Bisphosphonates (particularly clodronate) have been shown to have anti-inflammatory effects in animal models of rheumatoid arthritis (RA), as well as in arthritis in humans. In adjuvant- and antigen-induced arthritis in rats, clodronate suppresses the inflammatory articular lesions in the inflamed joints [29], whilst in human RA, clodronate decreases the levels of interleukin (ILJ-1, tumor necrosis factor-alpha (TNFaand /1-microglobulin in the circulation [30]. In vitro, clodronate inhibits cytokine and nitric oxide (NO) release and inducible nitric oxide synthase (iNOS) expression in macrophage-like cells. 

Other components of the innate response include natural killer (NK) cells and a number of cytokines. NK cells lyse certain types of tumor cells and virally infected cells and are a rich source of immune interferon (interferon-y), which stimulates macrophages and T cells hence they are thought to play an important role in host resistance to both neoplastic and viral disease. Type I interferons (interferon a and interferon P) are produced by a number of different cell types and appear very rapidly after viral infection. Type I interferons inhibit viral replication, inhibit cell proliferation, and increase the lytic potential of NK cells and therefore play a role in controlling viral and neoplastic disease. Several cytokines are important in the initiation of inflammatory responses. Those that have received the most attention include tumor necrosis factor alpha (TNFa), interleukin (IL)-1, and IL-6. There are also a number of chemotactic cytokines (including IL-8), called chemokines, which help to mobilize immune cells to the site of injury. 

Stehlik C, de Martin R, Kumabashiri I, Schmid JA, Binder BR, Lipp J (1998) Nuclear factor (NF)-kappaB-regulated X-chromosome-linked iap gene expression protects endothelial cells from tumor necrosis factor alpha-induced apoptosis. J Exp Med 188 211-216 Stennicke HR, Deveraux QL, Humke EW, Reed JC, Dixit VM, Salvesen GS (1999) Caspase-9 ctin be activated without proteolytic processing. J Biol Chem 274 8359-8362 Sun XM, Butterworth M, MacFarlane M, Dubiel W, Ciechanover A, Cohen GM (2004) Caspase activation inhibits proteasome function during apoptosis. Mol Cell 14 81-93 Suzuki Y, Imai Y, Nakayama H, Takahashi K, Takio K, Takahashi R (2001) A serine protease, HtrA2, is released from the mitochondria and interacts with XIAP, inducing cell death. Mol Cell 8 613-621... 

Ferger B, Leng A, Mura A, Hengerer B, Feldon J (2004) Genetic ablation of tumor necrosis factor-alpha (TNF-alpha) and pharmacological inhibition of TNF-synthesis attenuates MPTP toxicity in mouse striatum. J Neurochem 89 822-833. 

Belkowski SM, Alicea C, Eisenstein TK, Adler MW, Rogers TJ (1995) Inhibition of interleukin-1 and tumor necrosis factor-alpha synthesis following treatment of macrophages with the kappa opioid agonist U50, 488H. J Pharmacol Exp Ther 273 1491-1496. 

---