腫瘍壊死因子 TNF
WordNet
- be a contributing factor; "make things factor into a companys profitability"
- any of the numbers (or symbols) that form a product when multiplied together
- an independent variable in statistics
- anything that contributes causally to a result; "a number of factors determined the outcome"
- consider as relevant when making a decision; "You must factor in the recent developments" (同)factor in, factor out
- resolve into factors; "a quantum computer can factor the number 15" (同)factor in, factor out
- an event known to have happened or something known to have existed; "your fears have no basis in fact"; "how much of the story is fact and how much fiction is hard to tell"
- a concept whose truth can be proved; "scientific hypotheses are not facts"
- a piece of information about circumstances that exist or events that have occurred; "first you must collect all the facts of the case"
- a statement or assertion of verified information about something that is the case or has happened; "he supported his argument with an impressive array of facts"
- the localized death of living cells (as from infection or the interruption of blood supply) (同)mortification, gangrene, sphacelus
- an abnormal new mass of tissue that serves no purpose (同)tumour, neoplasm
PrepTutorEJDIC
- (…の)『要因』,(…を生み出す)要素《+『in』+『名』(do『ing』)》 / 囲数,約数 / 代理人,《おもに英》仲買人 / =factorize
- 〈C〉『事実』,実際にある(あった)事 / 〈U〉真相,真実(truth) / 《the~》(法律用語で)犯行
- 壊疽(えそ)
Wikipedia preview
出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2016/09/07 21:51:26」(JST)
[Wiki en表示]
"TNF" redirects here. For other uses, see TNF (disambiguation).
| TNF (Tumor Necrosis Factor) family |
|
Trimeric structure of TNF alpha, produced by Mus musculus, based on PDB structure 2TNF (1.4 Å Resolution). Different colors represent different monomers. Baeyens, KJ et al. (1999).[1] Figure rendered using FirstGlance Jmol.
|
| Identifiers |
| Symbol |
TNF |
| Pfam |
PF00229 |
| InterPro |
IPR006052 |
| PROSITE |
PDOC00224 |
| SCOP |
1tnf |
| SUPERFAMILY |
1tnf |
| OPM superfamily |
357 |
| OPM protein |
2hew |
| Available protein structures: |
| Pfam |
structures |
| PDB |
RCSB PDB; PDBe; PDBj |
| PDBsum |
structure summary |
|
| TNF |
|
crystal structure of trail-sdr5
|
| Identifiers |
| Symbol |
TNF |
| Pfam |
PF00229 |
| Pfam clan |
CL0100 |
| InterPro |
IPR006052 |
| PROSITE |
PDOC00561 |
| SCOP |
1tnr |
| SUPERFAMILY |
1tnr |
| Available protein structures: |
| Pfam |
structures |
| PDB |
RCSB PDB; PDBe; PDBj |
| PDBsum |
structure summary |
|
The tumor necrosis factor (TNF) superfamily refers to a group of cytokines that can cause cell death (apoptosis).
The first two members of the family to be identified were:
- Tumor necrosis factor (TNF), formerly known as TNFα or TNF alpha, is the best-known member of this class. TNF is a monocyte-derived cytotoxin that has been implicated in tumor regression, septic shock, and cachexia.[2][3] The protein is synthesized as a prohormone with an unusually long and atypical signal sequence, which is absent from the mature secreted cytokine.[4] A short hydrophobic stretch of amino acids serves to anchor the prohormone in lipid bilayers.[5] Both the mature protein and a partially processed form of the hormone can be secreted after cleavage of the propeptide.[5]
- Lymphotoxin-alpha, formerly known as Tumor necrosis factor-beta (TNF-β), is a cytokine that is inhibited by interleukin 10.[6]
Contents
- 1 Family members
- 2 Examples
- 3 Notes and references
- 4 External links
Family members
Nineteen proteins have been identified as part of the TNF family on the basis of sequence, functional, and structural similarities.[7] They include:[8][9][10]
- Tumor necrosis factor (TNF) (also known as cachectin [11] or TNF alpha)[12][13] is a cytokine that has a wide variety of functions. It can cause cytolysis of certain tumor cell lines; it is involved in the induction of cachexia; it is a potent pyrogen, causing fever by direct action or by stimulation of interleukin-1 secretion; it can stimulate cell proliferation and induce cell differentiation under certain conditions.
- Lymphotoxin-alpha (LT-alpha) and lymphotoxin-beta (LT-beta), two related cytokines produced by lymphocytes that are cytotoxic for a wide range of tumor cells in vitro and in vivo.[14]
- T cell antigen gp39 (CD40L), a cytokine that seems to be important in B-cell development and activation.
- CD27L, a cytokine that plays a role in T-cell activation. It induces the proliferation of co-stimulated T cells and enhances the generation of cytolytic T cells.
- CD30L, a cytokine that induces proliferation of T cells.
- FASL, a cell surface protein involved in cell death.[15]
- 4-1BBL, an inducible T cell surface molecule that contributes to T-cell stimulation.
- OX40L, a cell surface protein that co-stimulates T cell proliferation and cytokine production.[16]
- TNF-related apoptosis inducing ligand (TRAIL), a cytokine that induces apoptosis.[17]
Model of hydrogen bond between Asn34 of subunit A and Arg82 of subunit C, produced by
M. musculus, based on PDB structure 2TNF. The residues participating the hydrogen bond are shown in stick. The short bond length, 2.84Å, highly suggests a strong hydrogen bond that supports the tertiary structure. Baeyens, KJ et al. (1999).
[1] Generated in Chimera.
All these cytokines seem to form homotrimeric (or heterotrimeric in the case of LT-alpha/beta) complexes that are recognized by their specific receptors. Strong hydrogen bonds between the monomers stabilize the tertiary structure. One such example is the Asn34-Arg82 hydrogen bond in the M. musculus TNF alpha.[1] The PROSITE pattern for this family is located in a beta-strand in the central section of the protein that is conserved across all members.
All members of the TNF family, with the exception of the secreted lymphotoxin and a proliferation-inducing ligand (APRIL), are type II transmembrane proteins that protrude from immune cells. Such membrane-bound TNF ligands frequently signal back to the immune cells when they contact and bind their cognate receptors on other cells.[7]
Examples
Human proteins containing this domain include:
- CD40LG (TNFSF5); CD70 (TNFSF7); EDA; FASLG (TNFSF6); LTA (TNFSF1); LTB (TNFSF3);
- TNF
- TNFSF4 (OX40L); TNFSF8 (CD153); TNFSF9; TNFSF10 (TRAIL); TNFSF11 (RANKL); TNFSF12 (TWEAK); TNFSF13; TNFSF13B; TNFSF14; TNFSF15; TNFSF18;
Notes and references
This article incorporates text from the public domain Pfam and InterPro IPR006052
- ^ a b c Baeyens KJ, De Bondt HL, Raeymaekers A, Fiers W, De Ranter CJ (April 1999). "The structure of mouse tumour-necrosis factor at 1.4 Å resolution: towards modulation of its selectivity and trimerization". Acta Crystallogr. D. 55 (Pt 4): 772–8. doi:10.1107/s0907444998018435. PMID 10089307.
- ^ Fransen L, Müller R, Marmenout A, Tavernier J, Van der Heyden J, Kawashima E, Chollet A, Tizard R, Van Heuverswyn H, Van Vliet A (June 1985). "Molecular cloning of mouse tumour necrosis factor cDNA and its eukaryotic expression". Nucleic Acids Res. 13 (12): 4417–29. doi:10.1093/nar/13.12.4417. PMC 321797. PMID 2989794.
- ^ Kriegler M, Perez C, DeFay K, Albert I, Lu SD (April 1988). "A novel form of TNF/cachectin is a cell surface cytotoxic transmembrane protein: ramifications for the complex physiology of TNF". Cell. 53 (1): 45–53. doi:10.1016/0092-8674(88)90486-2. PMID 3349526.
- ^ Sherry B, Jue DM, Zentella A, Cerami A (December 1990). "Characterization of high molecular weight glycosylated forms of murine tumor necrosis factor". Biochem. Biophys. Res. Commun. 173 (3): 1072–8. doi:10.1016/S0006-291X(05)80895-2. PMID 2268312.
- ^ a b Cseh K, Beutler B (September 1989). "Alternative cleavage of the cachectin/tumor necrosis factor propeptide results in a larger, inactive form of secreted protein". J. Biol. Chem. 264 (27): 16256–60. PMID 2777790.
- ^ Waltenbaugh C, Doan T, Melvold R, Viselli S (2008). Immunology. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins. p. 68. ISBN 0-7817-9543-5.
- ^ a b Sun M, Fink PJ (2007). "A new class of reverse signaling costimulators belongs to the TNF family". J Immunol. 179 (7): 4307–12. doi:10.4049/jimmunol.179.7.4307. PMID 17878324.
- ^ Peitsch MC, Jongeneel CV (February 1993). "A 3-D model for the CD40 ligand predicts that it is a compact trimer similar to the tumor necrosis factors". Int. Immunol. 5 (2): 233–8. doi:10.1093/intimm/5.2.233. PMID 8095800.
- ^ Farrah T, Smith CA (July 1992). "Emerging cytokine family". Nature. 358 (6381): 26. doi:10.1038/358026b0. PMID 1377364.
- ^ Bazan JF (September 1993). "Emerging families of cytokines and receptors". Curr. Biol. 3 (9): 603–6. doi:10.1016/0960-9822(93)90009-D. PMID 15335677.
- ^ D. CAPUT, et al., Identification of a common nucleotide sequence in the 3'-untranslated region of mRNA molecules specifying inflammatory mediators, Proc. Natl. Acad. Sci. USA 83:1670-1674 Biochemistry, 1986 and references cited)
- ^ Beutler B, Cerami A (October 1988). "The history, properties, and biological effects of cachectin". Biochemistry. 27 (20): 7575–82. doi:10.1021/bi00420a001. PMID 3061461.
- ^ Vilcek J, Lee TH (April 1991). "Tumor necrosis factor. New insights into the molecular mechanisms of its multiple actions". J. Biol. Chem. 266 (12): 7313–6. PMID 1850405.
- ^ Browning JL, Ngam-ek A, Lawton P, DeMarinis J, Tizard R, Chow EP, Hession C, O'Brine-Greco B, Foley SF, Ware CF (March 1993). "Lymphotoxin beta, a novel member of the TNF family that forms a heteromeric complex with lymphotoxin on the cell surface". Cell. 72 (6): 847–56. doi:10.1016/0092-8674(93)90574-A. PMID 7916655.
- ^ Suda T, Takahashi T, Golstein P, Nagata S (December 1993). "Molecular cloning and expression of the Fas ligand, a novel member of the tumor necrosis factor family". Cell. 75 (6): 1169–78. doi:10.1016/0092-8674(93)90326-L. PMID 7505205.
- ^ Baum PR, Gayle RB, Ramsdell F, Srinivasan S, Sorensen RA, Watson ML, Seldin MF, Baker E, Sutherland GR, Clifford KN (September 1994). "Molecular characterization of murine and human OX40/OX40 ligand systems: identification of a human OX40 ligand as the HTLV-1-regulated protein gp34". EMBO J. 13 (17): 3992–4001. PMC 395319. PMID 8076595.
- ^ Wiley SR, Schooley K, Smolak PJ, Din WS, Huang CP, Nicholl JK, Sutherland GR, Smith TD, Rauch C, Smith CA (December 1995). "Identification and characterization of a new member of the TNF family that induces apoptosis". Immunity. 3 (6): 673–82. doi:10.1016/1074-7613(95)90057-8. PMID 8777713.
External links
- Tumor Necrosis Factors at the US National Library of Medicine Medical Subject Headings (MeSH)
- pex1 tumor necrosis factor gene
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Cell signaling: cytokines
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| By family |
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By function/
cell |
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TNF receptor superfamily modulators
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| LTB (TNFβ) |
- Agonists: Lymphotoxin (α (TNFβ), β (TNFC))
- Decoy receptors: Baminercept
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| TNF (TNFα) |
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TNFR1
|
- Agonists: Plusonermin
- Sonermin
- Tasonfermin
- TNF (TNFα)
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TNFR2
|
- Agonists: Plusonermin
- Sonermin
- Tasonfermin
- TNF (TNFα)
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Ungrouped
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- Antibodies: Adalimumab
- Afelimomab
- Certolizumab pegol
- Golimumab
- Infliximab
- Nerelimomab
- Ozoralizumab
- Remtolumab
- Placulumab
- Decoy receptors: Etanercept
- Lenercept
- Onercept
- Pegsunercept
- Enzyme inhibitors: Apratastat
- Other inhibitors: Apremilast
- Bupropion
- Catechins (green tea)
- Cannabinoids (cannabis, Echinacea purpurea)
- Curcumin (turmeric)
- LA-SS-Az
- Lenalidomide
- LSD
- Pentoxifylline
- Pomalidomide
- R-DOI
- TCB-2
- Thalidomide
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|
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| Others |
- TNF superfamily protein ligands: 4-1BBL (CD137L, TNFSF9)
- APRIL (CD256, TNFSF13)
- BAFF (CD257, TNFSF13B)
- CAML
- CD70 (CD27L, TNFSF7)
- CD153 (CD30L, TNFSF8)
- CD154 (CD40L, TNFSF5)
- Ectodysplasin (A, A2)
- FasL (CD95L, TNFSF6)
- GITRL (TNFSF18)
- LIGHT (HEVML, CD258, TNFSF14)
- OX40L (CD252, TNFSF4)
- RANKL (TRANCE, OPGL, ODF, CD254, TNFSF11)
- Siva (CD27BP)
- TRAIL (CD253, TNFSF10)
- TWEAK (TNFSF12)
- VEGI (TL1A, TNFSF15)
- Recombinant proteins: Ardenermin
- Dulanermin
- Antibodies: Belimumab
- Brentuximab vedotin
- Conatumumab
- Dacetuzumab
- Denosumab
- Drozitumab
- Enavatuzumab
- Iratumumab
- Lexatumumab
- Lucatumumab
- Mapatumumab
- Oxelumab
- Ruplizumab
- Tabalumab
- Tavolixizumab
- Teneliximab
- Tigatuzumab
- Toralizumab
- Urelumab
- Utomilumab
- Varlilumab
- Vorsetuzumab
- Vorsetuzumab mafodotin
- Decoy receptors: Briobacept
- Other inhibitors: Blisibimod
|
|
- See also: Cytokine receptor modulators
- Peptide receptor modulators
|
UpToDate Contents
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English Journal
- Fatty Acid synthase inhibitor c75 ameliorates experimental colitis.
- Matsuo S1, Yang WL2, Aziz M2, Kameoka S3, Wang P2.Author information 1Department of Surgery, Hofstra North Shore-Long Island Jewish School of Medicine, and The Feinstein Institute for Medical Research, Manhasset, New York, United States of America Department of Surgery II, Tokyo Women's Medical University, Tokyo, Japan.2Department of Surgery, Hofstra North Shore-Long Island Jewish School of Medicine, and The Feinstein Institute for Medical Research, Manhasset, New York, United States of America.3Department of Surgery II, Tokyo Women's Medical University, Tokyo, Japan.AbstractAbnormalities of lipid metabolism through overexpression of fatty acid synthase (FASN), which catalyzes the formation of long-chain fatty acids, are associated with the development of inflammatory bowel disease (IBD). C75 is a synthetic α-methylene-γ-butyrolactone compound that inhibits FASN activity. We hypothesized that C75 treatment could effectively reduce the severity of experimental colitis. Male C57BL/6 mice were fed 4% dextran sodium sulfate (DSS) for 7 d. C75 (5 mg/kg body weight) or dimethyl sulfoxide (DMSO) (vehicle) was administered intraperitoneally from d 2 to 6. Clinical parameters were monitored daily. Mice were euthanized on d 8 for histological evaluation and measurements of colon length, chemokine, cytokine and inflammatory mediator expression. C75 significantly reduced body weight loss from 23% to 15% on d 8, compared with the vehicle group. The fecal bleeding, diarrhea and colon histological damage scores in the C75-treated group were significantly lower than scores in the vehicle animals. Colon shortening was significantly improved after C75 treatment. C75 protected colon tissues from DSS-induced apoptosis by inhibiting caspase-3 activity. Macrophage inflammatory protein 2, keratinocyte-derived chemokine, myeloperoxidase activity and proinflammatory cytokines (tumor necrosis factor-α, interleukin [IL]-1β and IL-6) in the colon were significantly downregulated in the C75-treated group, compared with the vehicle group. Treatment with C75 in colitis mice inhibited the elevation of FASN, cyclooxygenase-2 and inducible nitric oxide synthase expression as well as IκB degradation in colon tissues. C75 administration alleviates the severity of colon damage and inhibits the activation of inflammatory pathways in DSS-induced colitis. Thus, inhibition of FASN may represent an attractive therapeutic potential for treating IBD.
- Molecular medicine (Cambridge, Mass.).Mol Med.2014 Dec 24;20(1):1-9. doi: 10.2119/molmed.2013.00113.
- Abnormalities of lipid metabolism through overexpression of fatty acid synthase (FASN), which catalyzes the formation of long-chain fatty acids, are associated with the development of inflammatory bowel disease (IBD). C75 is a synthetic α-methylene-γ-butyrolactone compound that inhibits FASN activ
- PMID 24306512
- Toxicity and bio-accumulation of inhaled cerium oxide nanoparticles in CD1 mice.
- Aalapati S1, Ganapathy S, Manapuram S, Anumolu G, Prakya BM.Author information 1Department of Toxicology, International Institute of Biotechnology and Toxicology [IIBAT] , Chennai , India.AbstractMale CD1 mice were subjected to nose-inhalation exposure of CeO2 nanoparticles (NPs) for 0, 7, 14 or 28 days with 14 or 28 days of recovery time at an aerosol concentration of 2 mg/m(3). Markers of lung injury and pro-inflammatory cytokines (interleukin-1beta, tumour necrosis factor-alpha, interleukin-6 and macrophage inflammatory protein-2) in bronchoalveolar lavage fluid (BALF), oxidative stress in lungs, bio-accumulation, and histopathology of pulmonary and extrapulmonary tissues were assessed. BALF analysis revealed the induction of pulmonary inflammation, as evident by an increase in the influx of neutrophils with a significant secretion of pro-inflammatory cytokines that lead to generation of oxidative stress and cytotoxicity, as is evident by induction of lipid peroxidation, depletion of glutathione and increased BALF lactate dehydrogenase and protein. The histopathological examination revealed that these inhaled CeO2 NPs were located all over the pulmonary parenchyma, inducing a severe, chronic, active inflammatory response characterised by necrosis, proteinosis, fibrosis and well-formed discrete granulomas in the pulmonary tissue and tubular degeneration leading to coagulative necrosis in kidneys. Inductively coupled plasma optical emission spectrometer results showed a significant bio-accumulation of these particles in the pulmonary and extrapulmonary tissues, even after one month of post-inhalation exposure. Together, these findings suggest that inhalation exposure of CeO2 NPs can induce pulmonary and extrapulmonary toxicity.
- Nanotoxicology.Nanotoxicology.2014 Nov;8(7):786-98. doi: 10.3109/17435390.2013.829877. Epub 2013 Aug 22.
- Male CD1 mice were subjected to nose-inhalation exposure of CeO2 nanoparticles (NPs) for 0, 7, 14 or 28 days with 14 or 28 days of recovery time at an aerosol concentration of 2 mg/m(3). Markers of lung injury and pro-inflammatory cytokines (interleukin-1beta, tumour necrosis factor-alpha, interleuk
- PMID 23914771
- The probiotic Lactobacillus coryniformis CECT5711 reduces the vascular pro-oxidant and pro-inflammatory status in obese mice.
- Toral M1, Gómez-Guzmán M1, Jiménez R, Romero M, Sánchez M1, Utrilla MP, Garrido-Mesa N2, Rodríguez-Cabezas ME, Olivares M3, Gálvez J, Duarte J.Author information 1*Department of Pharmacology, School of Pharmacy, University of Granada, Granada, Spain.2‡CIBER-EHD, Department of Pharmacology, Center for Biomedical Research, University of Granada, Granada, Spain.3§Research Department of Biosearch, Granada, Spain.AbstractObesity is associated with intestine dysbiosis and is characterized by a low-grade inflammatory status, which affects vascular function. In the present study, we evaluated the effects of a probiotic with immunomodulatory properties, Lactobacillus coryniformis CECT5711, in obese mice fed on an HFD (high-fat diet). The probiotic treatment was given for 12 weeks, and it did not affect the weight evolution, although it reduced basal glycaemia and insulin resistance. L. coryniformis administration to HFD-induced obese mice induced marked changes in microbiota composition and reduced the metabolic endotoxaemia as it decreased the LPS (lipopolysaccharide) plasma level, which was associated with a significant improvement in gut barrier disruption. Furthermore, it lowered TNFα (tumour necrosis factor α) expression in liver, improving the inflammatory status, and thus the glucose metabolism. Additionally, the probiotic reversed the endothelial dysfunction observed in obese mice when endothelium- and NO (nitric oxide)-dependent vasodilatation induced by acetylcholine in aortic rings was studied. It also restored the increased vessel superoxide levels observed in obese mice, by reducing NADPH oxidase activity and increasing antioxidant enzymes. Moreover, chronic probiotic administration for 2 weeks also improved endothelial dysfunction and vascular oxidative stress induced by in vivo administration of LPS in control mice fed on a standard chow diet. The results of the present study demonstrate an endothelial-protective effect of L. coryniformis CECT5711 in obese mice by increasing NO bioavailability, suggesting the therapeutic potential of this gut microbiota manipulation to prevent vasculopathy in obesity.
- Clinical science (London, England : 1979).Clin Sci (Lond).2014 Jul 1;127(1):33-45. doi: 10.1042/CS20130339.
- Obesity is associated with intestine dysbiosis and is characterized by a low-grade inflammatory status, which affects vascular function. In the present study, we evaluated the effects of a probiotic with immunomodulatory properties, Lactobacillus coryniformis CECT5711, in obese mice fed on an HFD (h
- PMID 24410749
Japanese Journal
- The Role of Kupffer Cells in Carbon Tetrachloride Intoxication in Mice
- Kiso Kaori,Ueno Satoko,Fukuda Mana [他]
- Biological & pharmaceutical bulletin 35(6), 980-983, 2012-06
- NAID 40019278292
- Lipopolysaccharide Induces Disruption of the Tight Junction via Toll-Like Receptor 4 and Tumor Necrosis Factor Alpha
- Shiga Hiroshi,Aoyagi Kunihiko,Morita Isamu,Hayashi Yoshihiro,Sakisaka Shotaro
- 福岡大学医学紀要 39(2), 95-102, 2012-06
- NAID 110009422836
Related Links
- factor [fak´ter] an agent or element that contributes to the production of a result. accelerator factor factor V, one of the coagulation factors. factor I see ... Certain cytokines (interleukin [IL]-1 and tumor necrosis factor [TNF]-[alpha], but ...
- This gene encodes a multifunctional proinflammatory cytokine that belongs to the tumor necrosis factor (TNF) superfamily. This cytokine is mainly secreted by macrophages. It can bind to, and thus functions through its receptors ...
★リンクテーブル★
[★]
- 英
- tumor necrosis factor-α TNFα, tumor necrosis factor-alpha TNF-alpha
- 同
- 腫瘍壊死因子α、カケクチン cachectin
- 関
- サイトカイン
- 腫瘍壊死因子 tumor necrosis factor TNF
概念
- 活性化マクロファージなどが産生する抗腫瘍性サイトカイン
作用
- 視床下部に作用
[★]
- 英
- tumor necrosis factor receptor、TNF receptor, TNFR
- 同
- 腫瘍壊死因子レセプター、TNF受容体、TNFレセプター
- 関
- 腫瘍壊死因子 tumor necrosis factor TNF
[show details]
[★]
腫瘍壊死因子 tumor necrosis factor
[★]
- 関
- tumor necrosis factor
[★]
- 関
- TNF receptor-associated factor、TRAF、tumor necrosis factor receptor-associated peptides and proteins
[★]
腫瘍壊死因子受容体メンバー14
[★]
- 関
- actual、actually、in fact、in practice、indeed、practically
[★]
- 関
- element、elementary、factorial、parameter
[★]
[★]
- 同
- Tumor necrosis factors