肿瘤坏死因子

肿瘤坏死因子（TNF）旧称肿瘤坏死因子-α（TNF-α）^[1]以区别肿瘤坏死因子-β，属肿瘤坏死因子超家族一员，是一种涉及到系统性炎症的细胞因子，同时也是属于引起急相反应（英语：Acute-phase protein）的众多细胞因子中的一员。主要由巨噬细胞分泌，不过有一些其它类型的细胞也能生产。

肿瘤坏死因子
PDB rendering based on 1TNF.
有效结构 PDB 直系同源检索：PDBe, RCSB PDB查询代码列表 1A8M, 1TNF, 2AZ5, 2E7A, 2TUN, 2ZJC, 2ZPX, 3ALQ, 3IT8, 3L9J, 4TSV, 5TSW
标识
代号	TNF; DIF; TNF-alpha; TNFA; TNFSF2
扩展标识	遗传学：191160 鼠基因：104798 同源基因：496 ChEMBL: 1825 GeneCards: TNF Gene
基因本体论描述 分子功能 · protease binding · cytokine activity · tumor necrosis factor receptor binding · protein binding · identical protein binding · transcription regulatory region DNA binding 细胞成分 · phagocytic cup · extracellular space · plasma membrane · integral to plasma membrane · external side of plasma membrane · cell surface · membrane raft · recycling endosome 生物过程 · protein import into nucleus, translocation · negative regulation of transcription from RNA polymerase II promoter · MAPK cascade · activation of MAPKKK activity · activation of MAPK activity · response to hypoxia · cell activation · positive regulation of cytokine production · positive regulation of protein phosphorylation · negative regulation of L-glutamate transport · chronic inflammatory response to antigenic stimulus · negative regulation of cytokine secretion involved in immune response · positive regulation of chronic inflammatory response to antigenic stimulus · positive regulation of humoral immune response mediated by circulating immunoglobulin · skeletal muscle contraction · glucose metabolic process · apoptotic process · anti-apoptosis · induction of apoptosis · activation of cysteine-type endopeptidase activity involved in apoptotic process · transformed cell apoptotic process · inflammatory response · humoral immune response · JNK cascade · negative regulation of cell proliferation · induction of apoptosis by extracellular signals · induction of apoptosis by extracellular signals · induction of apoptosis via death domain receptors · response to mechanical stimulus · response to virus · response to salt stress · organ morphogenesis · negative regulation of gene expression · negative regulation of alkaline phosphatase activity · negative regulation of lipid storage · positive regulation of necrotic cell death · response to activity · calcium-mediated signaling · extracellular matrix organization · sequestering of triglyceride · positive regulation of protein complex assembly · positive regulation of fever generation · lipopolysaccharide-mediated signaling pathway · negative regulation of interleukin-6 production · positive regulation of chemokine production · positive regulation of interferon-gamma production · positive regulation of interleukin-6 production · receptor biosynthetic process · positive regulation of peptidyl-serine phosphorylation · tumor necrosis factor-mediated signaling pathway · positive regulation of heterotypic cell-cell adhesion · positive regulation of NF-kappaB import into nucleus · response to drug · positive regulation of apoptotic process · positive regulation of apoptotic process · negative regulation of apoptotic process · positive regulation of programmed cell death · regulation of I-kappaB kinase/NF-kappaB cascade · positive regulation of I-kappaB kinase/NF-kappaB cascade · positive regulation of protein complex disassembly · positive regulation of MAP kinase activity · protein kinase B signaling cascade · positive regulation of neuron apoptotic process · negative regulation of growth of symbiont in host · negative regulation of viral genome replication · positive regulation of chemokine biosynthetic process · positive regulation of interleukin-8 biosynthetic process · positive regulation of nitric oxide biosynthetic process · negative regulation of fat cell differentiation · negative regulation of osteoblast differentiation · positive regulation of osteoclast differentiation · positive regulation of mitosis · negative regulation of transcription, DNA-dependent · positive regulation of transcription, DNA-dependent · positive regulation of transcription from RNA polymerase II promoter · positive regulation of transcription from RNA polymerase II promoter · positive regulation of translational initiation by iron · negative regulation of glucose import · positive regulation of JNK cascade · embryonic digestive tract development · positive regulation of smooth muscle cell proliferation · positive regulation of cytokine secretion · regulation of insulin secretion · positive regulation of synaptic transmission · defense response to Gram-positive bacterium · leukocyte tethering or rolling · negative regulation of lipid catabolic process · regulation of immunoglobulin secretion · positive regulation of membrane protein ectodomain proteolysis · positive regulation of sequence-specific DNA binding transcription factor activity · positive regulation of NF-kappaB transcription factor activity · positive regulation of protein transport · response to glucocorticoid stimulus · positive regulation of NFAT protein import into nucleus · positive regulation of hair follicle development · positive regulation of protein kinase B signaling cascade · induction of necroptosis by extracellular signals · positive regulation of vitamin D biosynthetic process · positive regulation of calcidiol 1-monooxygenase activity · epithelial cell proliferation involved in salivary gland morphogenesis · regulation of branching involved in salivary gland morphogenesis · negative regulation of branching involved in lung morphogenesis · necrotic cell death · positive regulation of ERK1 and ERK2 cascade · cellular response to amino acid stimulus · cellular response to nicotine · cellular response to organic cyclic compound · positive regulation of mononuclear cell migration · positive regulation of podosome assembly · extrinsic apoptotic signaling pathway · positive regulation of protein localization at cell surface · positive regulation of chemokine (C-X-C motif) ligand 2 production Sources: Amigo / QuickGO
RNA表达模式
更多表达数据
直系同源体
物种	人类	小鼠
Entrez	7124	21926
Ensembl	ENSG00000204490	ENSMUSG00000024401
UniProt	P01375	P06804
mRNA序列	NM_000594.3	NM_013693.2
蛋白序列	NP_000585.2	NP_038721.1
基因位置	Chr 6: 31.54 – 31.55 Mb	Chr 17: 35.2 – 35.2 Mb
PubMed查询	[1]	[2]
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功能

总括而言，肿瘤坏死因子能抑制不同种流感病毒的复制，拥有强大的抗病毒效果^[2]。肿瘤坏死因子的主要作用是调节免疫细胞的功能。作为一种内源性致热原，它能够促使发热，引起细胞凋亡，（通过诱使产生IL1和IL6（英语：Interleukin 6））引发败血症，引起恶病体质，引发炎症，阻止肿瘤发生和病毒复制（英语：Viral replication）。

肿瘤坏死因子生产的失调被认为与许多人类疾病有关，包括阿茲海默症^[3]、癌症^[4]、重性抑郁障碍^[5]和肠炎。^[6]虽然仍有争议，不过当前的研究认为肿瘤坏死因子α的水平与抑郁和肠炎有关。^[7]基因工程生产的肿瘤坏死因子被用作免疫兴奋剂（英语：Immunostimulant）（国际非专利药品名称为他索纳明）。肿瘤的恶变过程中，肿瘤坏死因子α常异位表达，而其过量表达同甲状旁腺激素一道与引发继发性高钙血症和癌症有关。

炎症过程中释放的TNF与H2O2诱导的BCa转化有关，伴血吸虫感染的BCa患者血清中TNF水平显著升高。另外，T3及T4期患者TNF水平高于T1及T2早期患者，提示TNF水平可能有助于BCa的进展^[8]。由于TNF有助于BCa的形成和发展，故而可以作为评估BCa侵袭性和恶性程度的指标^[9]。

参考文献

1. Liu CY, Tam SS, Huang Y, Dubé PE, Alhosh R, Girish N, Punit S, Nataneli S, Li F, Bender JM, Washington MK, Polk DB. TNF Receptor 1 Promotes Early-Life Immunity and Protects against Colitis in Mice. Cell Rep. 2020 Oct 20;33(3):108275. doi: 10.1016/j.celrep.2020.108275. PMID 33086075; PMCID: PMC7682618.
2. Seo, S. H.; Webster, R. G. Tumor Necrosis Factor Alpha Exerts Powerful Anti-Influenza Virus Effects in Lung Epithelial Cells. Journal of Virology. 2002-02-01, 76 (3): 1071–1076. ISSN 0022-538X. doi:10.1128/jvi.76.3.1071-1076.2002.
3. Swardfager W, Lanctôt K, Rothenburg L, Wong A, Cappell J, Herrmann N. A meta-analysis of cytokines in Alzheimer's disease. Biol Psychiatry. 2010, 68 (10): 930–941. PMID 20692646. doi:10.1016/j.biopsych.2010.06.012.
4. Locksley RM, Killeen N, Lenardo MJ. The TNF and TNF receptor superfamilies: integrating mammalian biology. Cell. 2001, 104 (4): 487–501. PMID 11239407. doi:10.1016/S0092-8674(01)00237-9.
5. Dowlati Y, Herrmann N, Swardfager W, Liu H, Sham L, Reim EK, Lanctôt KL. A meta-analysis of cytokines in major depression. Biol Psychiatry. 2010, 67 (5): 446–457. PMID 20015486. doi:10.1016/j.biopsych.2009.09.033.
6. Brynskov J, Foegh P, Pedersen G, Ellervik C, Kirkegaard T, Bingham A, Saermark T. Tumour necrosis factor alpha converting enzyme (TACE) activity in the colonic mucosa of patients with inflammatory bowel disease. Gut. 2002, 51 (1): 37–43. PMC 1773288 . PMID 12077089. doi:10.1136/gut.51.1.37.
7. Mikocka-Walus AA, Turnbull DA, Moulding NT, Wilson IG, Andrews JM, Holtmann GJ. Controversies surrounding the comorbidity of depression and anxiety in inflammatory bowel disease patients: a literature review. Inflammatory Bowel Diseases. 2007, 13 (2): 225–234. PMID 17206706. doi:10.1002/ibd.20062.
8. 叶卫丰,贺敏,吴志斌.膀胱癌患者外周血中IL-2、IFN-γ、TNF的表达及临床意义.临床和实验医学杂志,2016,15(11):1064
9. 孙祖刚、刘硕等.炎症细胞和促炎性细胞因子在膀胱肿瘤炎症微环境中的作用概述.湖北科技学院学报(医学版).2018年，第5期：P451-454

参见

• 单株益生菌(Bifidobacterium animalis)

外部链接

• 医学主题词表（MeSH）：Tumor+Necrosis+Factor-alpha