腫瘤壞死因子

腫瘤壞死因子（TNF）舊稱腫瘤壞死因子-α（TNF-α）^[1]以區別腫瘤壞死因子-β，屬腫瘤壞死因子超家族一員，是一種涉及到系統性炎症的細胞因子，同時也是屬於引起急相反應（英語：Acute-phase protein）的眾多細胞因子中的一員。主要由巨噬細胞分泌，不過有一些其它類型的細胞也能生產。

腫瘤壞死因子
PDB rendering based on 1TNF.
有效結構 PDB 直系同源檢索：PDBe, RCSB PDB查詢代碼列表 1A8M, 1TNF, 2AZ5, 2E7A, 2TUN, 2ZJC, 2ZPX, 3ALQ, 3IT8, 3L9J, 4TSV, 5TSW
標識
代號	TNF; DIF; TNF-alpha; TNFA; TNFSF2
擴展標識	遺傳學：191160 鼠基因：104798 同源基因：496 ChEMBL: 1825 GeneCards: TNF Gene
基因本體論描述 分子功能 · protease binding · cytokine activity · tumor necrosis factor receptor binding · protein binding · identical protein binding · transcription regulatory region DNA binding 細胞成分 · phagocytic cup · extracellular space · plasma membrane · integral to plasma membrane · external side of plasma membrane · cell surface · membrane raft · recycling endosome 生物過程 · 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表達模式
更多表達數據
直系同源體
物種	人類	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查詢	[1]	[2]
閱 論 編

功能

總括而言，腫瘤壞死因子能抑制不同種流感病毒的複製，擁有強大的抗病毒效果^[2]。腫瘤壞死因子的主要作用是調節免疫細胞的功能。作為一種內源性致熱原，它能夠促使發燒，引起細胞凋亡，（通過誘使產生IL1和IL6（英語：Interleukin 6））引發敗血症，引起惡病體質，引發炎症，阻止腫瘤發生和病毒複製（英語：Viral replication）。

腫瘤壞死因子生產的失調被認為與許多人類疾病有關，包括阿茲海默症^[3]、癌症^[4]、重性抑鬱障礙^[5]和腸炎。^[6]雖然仍有爭議，不過當前的研究認為腫瘤壞死因子α的水平與抑鬱和腸炎有關。^[7]基因工程生產的腫瘤壞死因子被用作免疫興奮劑（英語：Immunostimulant）（國際非專利藥品名稱為他索納明）。腫瘤的惡變過程中，腫瘤壞死因子α常異位表達，而其過量表達同副甲狀腺激素一道與引發繼發性高鈣血症和癌症有關。

炎症過程中釋放的TNF與H2O2誘導的BCa轉化有關，伴血吸蟲感染的BCa患者血清中TNF水平顯著升高。另外，T3及T4期患者TNF水平高於T1及T2早期患者，提示TNF水平可能有助於BCa的進展^[8]。由於TNF有助於BCa的形成和發展，故而可以作為評估BCa侵襲性和惡性程度的指標^[9]。

參考文獻

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. 葉衛豐,賀敏,吳志斌.膀胱癌患者外周血中IL-2、IFN-γ、TNF的表達及臨床意義.臨床和實驗醫學雜誌,2016,15(11):1064
9. 孫祖剛、劉碩等.炎症細胞和促炎性細胞因子在膀胱腫瘤炎症微環境中的作用概述.湖北科技學院學報(醫學版).2018年，第5期：P451-454

參見

• 單株益生菌(Bifidobacterium animalis)

外部連結

• 醫學主題詞表（MeSH）：Tumor+Necrosis+Factor-alpha