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Details for messenger / hormone: TNF-alpha

EndoNet ID: ENH00200

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Synonyms

  • TNF-alpha
  • TNFA
  • TNF
  • tumor necrosis factor alpha
  • TNF alpha
  • cachectin
  • tumor necrosis factor
  • tumor necrosis factor ligand superfamily member 2
  • TNFSF2
  • TNFalpha
  • tumor necrosis factor, soluble form

General information

  • Estrogens as well as androgens inhibit the production of IL-1beta and TNF-alpha on monocyte-macrophages. [1]
  • The ligand dependent transactivation function of PPARgamma was suppressed by IL-1 and TNF-alpha. [2]
  • TNF-alpha is linked to the development of insulin resistance. [3]
  • TNF-alpha is a powerful local regulator within adipose tissue, acting in both an autocrine and a paracrine manner to influence a range of processes, including apoptosis. [3]
  • Inflammatory cytokine; adipokine [4]
  • Combined treatment of PPARgamma and cytokines (IL-1 or TNF-alpha) inhibited adipogenesis and induced osteoblastgenesis in bone marrow-derived mesenchymal stem cells. [2]
  • Inhibits the expression of the transcription factor CCAAT/enhancer binding protein alpha (CEBP alpha) and the nuclear receptor peroxisome proliferator-activated receptor gamma 2 (PPAR gamma 2). [5]
  • TNF alpha and IL-1 suppress adipogenesis through activation of the TAK1/TAB1/NIK cascade, which subsequently inhibits PPAR gamma activity. [6]
  • The soluble form derives from the membrane form by proteolytic processing. [7]
  • Tumor necrosis factor (TNF)-alpha-induced hepatocyte apoptosis is implicated in a wide range of liver diseases including viral hepatitis, alcoholic hepatitis, ischemia/reperfusion liver injury, and fulminant hepatic failure. [8]
  • TNF-alpha is a key regulator of the synthesis of IL-6, of the acute-phase protein, haptoglobin, and of the neurotrophin, nerve growth factor. [3]
  • Stimulate the synthesis of some of the positive, and inhibits negative acute phase proteins. [9]
  • Tumor necrosis factor-alpha (TNF-alpha) is one of a number of cytokines implicated in the progression of alcohol-induced liver disease. [10]
  • Stimulates the nuclear factor kappa beta transcription factor, which orchestrates a series of inflammatory events. [5]

Classification

Hormone function

  • development and growth
    • apoptosis
    • immune response
      • activation

      Chemical classification

      • hormone
        • genome-encoded
          • cytokines
            • TNF family

        Composition

        unprocessed membrane form

        Sequence
        MSTESMIRD VELAEEALP KKTGGPQGS 
        RRCLFLSLF SFLIVAGAT TLFCLLHFG 
        VIGPQREEF PRDLSLISP LAQAVRSSS 
        RTPSDKPVA HVVANPQAE GQLQWLNRR 
        ANALLANGV ELRDNQLVV PSEGLYLIY 
        SQVLFKGQG CPSTHVLLT HTISRIAVS 
        YQTKVNLLS AIKSPCQRE TPEGAEAKP 
        WYEPIYLGG VFQLEKGDR LSAEINRPD 
        YLDFAESGQ VYFGIIAL
        UniProt P01375

        soluble form

        Sequence
        VRSSSRTPS DKPVAHVVA NPQAEGQLQ 
        WLNRRANAL LANGVELRD NQLVVPSEG 
        LYLIYSQVL FKGQGCPST HVLLTHTIS 
        RIAVSYQTK VNLLSAIKS PCQRETPEG 
        AEAKPWYEP IYLGGVFQL EKGDRLSAE 
        INRPDYLDF AESGQVYFG IIAL

        Links to other resources

        UniProt P01375
        Ensembl ENST00000451263
        KEGG hsa:7124
        • Anatomical structure: adipose_tissue

          • Several inflammatory cytokines are now recognised to be expressed in, and secreted by, white adipocytes, the first to be identified being TNFα. [3]
        • Anatomical structure: fat_cell

          • Several inflammatory cytokines are now recognised to be expressed in, and secreted by, white adipocytes, the first to be identified being TNF-alpha. [3]
          • Adipocyte TNF-alpha action strikingly ameliorates the insulin resistance of murine obesity, but inhibition of TNF-alpha has a negligible effect on the insulin resistance of obese humans, because TNF-alpha is expressed at much lower levels in human adipose tissue. [11]
        • Anatomical structure: macrophage

          • In man, the secretion of TNFalpha is reported to be mainly due to the cells of the stromal vascular and matrix fractions, including the macrophages. [3]

          Influenced by:

          • TLR2
            in alveolar_macrophage
            • SP-A significantly reduced PGN-elicited tumor necrosis factor alpha (TNF-alpha) secretion by rat alveolar macrophages. The inhibitory effect on TNF-alpha secretion was dependent upon SP-A concentrations in physiological range. [12]
            • Direct interaction of SP-A with TLR2 alters PGN-induced cell signaling. [12]
        • Anatomical structure: Kupffer_cell_stellate_cell_of_liver

          • The cytokines of the acute phase reaction are synthesized in the Kupffer cells in the hepatic sinusoids. [9]
          • TNF-alpha is thought to regulate Kupffer cell activation through both autocrine and paracrine mechanisms. [13]

          Influenced by:

          • TLR4
            in Kupffer_cell_stellate_cell_of_liver
            • LPS activates Kupffer cells to produce mediators such as TNF-alpha. [14]
        • Anatomical structure: monocyte

          Influenced by:

          • EP4
            in monocyte
            • EP4 receptors are involved in the regulation of TNF-alpha production in monocytes. [15]
            • PGE1, PGE2 and cicaprost suppressed the elaboration of TNF-alpha in LPS-stimulated cells in a concentration-dependent manner. TNF-alpha generation was inhibited by 85 to 90% at the highest concentration (10 mM) of agonist tested. [16]
          • EP2
            in monocyte
            • PGE1, PGE2 and cicaprost suppressed the elaboration of TNF-alpha in LPS-stimulated cells in a concentration-dependent manner. TNF-alpha generation was inhibited by 85 to 90% at the highest concentration (10 mM) of agonist tested. [16]
        • Anatomical structure: osteoblast

        • Anatomical structure: hepatocyte

        • Anatomical structure: cell_of_endometrium_of_uterus

          • Is increased in the endometrium of women with menorrhagia. [17]
        • Anatomical structure: microglial_cell_in_central_nervous_system

          • Microglia produce molecules including NO and TNF-alpha that can be toxic to CNS cells including myelin-producing oligodendrocytes and neurons, which are compromised in the course of MS. [18]
        • Anatomical structure: peripheral blood mononuclear cell (PBMC)

          Influenced by:

          • TLR2
            in peripheral blood mononuclear cell (PBMC)
            • The products of gram-positive bacteria may be promoting increases in circulating TNF-alpha and soluble TNF-alpha receptor via stimulation of TLR-2. [19]
        • Anatomical structure: dendritic_cell_in_lymphoid_tissues

        • Anatomical structure: neutrophil_granulocyte

        • Anatomical structure: epithelial_cell

        • Anatomical structure: B-lymphocyte

        • Anatomical structure: placenta

          • TNF-alpha is synthesized and secreted from the placenta. [20]

        Targets

        CellADAM17TNFR1TNFR2
        adipose tissue Present
        Phenotypes
        • negative regulation of insulin receptor signaling pathway
        • regulation of glucose homeostasis
        • hyperinsulinemia
        • insulin resistance
        • negative regulation of gene expression
        • obesity
        Influences
        • leptin
        • insulin
        Present
        Influences
        • leptin
        astrocyte Present
        bone marrow Present
        Phenotypes
        • atherosclerosis
        brain Present
        bronchial epithelial cell Present
        Influences
        • IL-8
        cerebellar cortex Present
        cerebral cortex Present
        continuous vascular endothelial cell of blood vessels and lymphatics Present
        Phenotypes
        • regulation of angiogenesis
        dendritic cell in lymphoid tissues follicular Present
        epithelial cell Present
        epithelial cell with microvilli Present
        Influences
        • eotaxin
        • IL-8
        hepatocyte Present
        Phenotypes
        • antagonizing IL-1alpha/beta ligand activity
        • positive regulation of apoptosis
        • positive regulation of cell proliferation
        Influences
        • TGF-alpha
        • IL-1 alpha
        • IL-1 beta
        • IL-1RA
        Present
        Phenotypes
        • antagonizing IL-1alpha/beta ligand activity
        • positive regulation of cell proliferation
        • positive regulation of apoptosis
        Influences
        • TGF-alpha
        • IL-1 beta
        • IL-1 alpha
        • IL-1RA
        hippocampus Present
        keratinocyte Present
        Kupffer cell stellate cell of liver Present
        Present
        lipocyte of liver Present
        Influences
        • RANTES
        Present
        Influences
        • RANTES
        lung Present
        macrophage Present
        Present
        Influences
        • PAF
        monocyte Present
        Phenotypes
        • ectodomain shedding
        Present
        Influences
        • PAF
        neuron Present
        neutrophil granulocyte Present
        Phenotypes
        • ectodomain shedding
        Present
        Influences
        • IL-8
        Present
        osteoclast Present
        Present
        pneumocyte type II Present
        Influences
        • IL-8
        stromal fibroblast Present
        T-lymphocyte Present
        Phenotypes
        • ectodomain shedding
        uterus Present
        Reference