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Details for messenger / hormone: interleukin 6

EndoNet ID: ENH00165

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Synonyms

  • interleukin 6
  • Interleukin-6
  • IL-6
  • IL6
  • BSF-2
  • IL 6
  • B-cell stimulatory factor 2
  • interferon beta-2
  • hybridoma growth factor
  • CTL differentiation factor
  • CDF

General information

  • Enhance glucocorticoid production. [1]
  • Inflammatory cytokine, inducer of lyposis. [2]
  • Increased IL6 production in obesity in white adipose tissue. [3]
  • Both plasma levels of IL-6 and expression in WAT are elevated in obesity and insulin resistance. [4]
  • IL6 exhibits pleiotropic effects on a variety of tissues, including down regulation of adipocyte LPL, elevation of lipolytic activity, stimulation of acute phase protein synthesis, activation of the hypothalamic-pituitary axis and thermogenesis. [3]
  • Autocrine products of osteoclasts such as interleukin-6 may play an important role in normal osteoclast formation and activity. [5]
  • IL6, secreted from epithelial cells or macrophages, induces WNT5A upregulation in mesenchymal cells. [6]
  • IL-6 is capable of inhibiting p53-induced apoptosis in myeloid leukemic cells. [7]
  • While TNF alpha, noradrenaline, isoprenaline and beta-adrenergic receptor activation stimulate IL6 gene expression and protein secretion, dexamethason markedly suppresses its production. [3]
  • Overproduction of IL-6 is associated with a spectrum of age-related conditions including cardiovascular disease, osteoporosis, arthritis, type 2 diabetes, certain cancers, periodontal disease, frailty, and functional decline. [8]
  • Stimulates type-2 acute phase proteins, such as fibrinogen, alpha-1-antitrypsin, haptoglobin and ceruloplasmin. [9]
  • IL-6 inhibits insulin receptor signal transduction and downstream insulin action, particularly glycogen synthesis. [10]

Classification

Hormone function

  • immune response
    • activation

    Chemical classification

    • hormone
      • genome-encoded
        • cytokines
          • IL-6-type cytokines

      Composition

      mature peptide

      Sequence
      VPPGEDSKD VAAPHRQPL TSSERIDKQ 
      IRYILDGIS ALRKETCNK SNMCESSKE 
      ALAENNLNL PKMAEKDGC FQSGFNEET 
      CLVKIITGL LEFEVYLEY LQNRFESSE 
      EQARAVQMS TKVLIQFLQ KKAKNLDAI 
      TTPDPTTNA SLLTKLQAQ NQWLQDMTT 
      HLILRSFKE FLQSSLRAL RQM

      Links to other resources

      UniProt P05231
      Ensembl ENST00000404625
      KEGG hsa:3569
      • Anatomical structure: fat_cell

        • IL-6 is expressed in, and secreted by, adipocytes. [4]

        Influenced by:

        • biliary glycoprotein 1
          in neutrophil_granulocyte
          • Evidence in mice suggests that biliary glycoprotein activation on murine dendritic cells causes IL-6 and IL-12 release. [11]
      • Anatomical structure: adipose_tissue

        • Ten to thirty-five percent of the body's basal circulating IL-6 is derived from adipose tissue. [10]
        • IL-6 is expressed in, and secreted by, adipocytes. [4]

        Influenced by:

        • ACTH receptor
          in adipose_tissue
          • Melanocortins induce interleukin 6 gene expression and secretion through melanocortin receptor 2 and 5 in adipocytes. [12]
          • Function of melanocortins in regulating Il6 gene expression and production in adipocytes through membrane receptors which are called melanocortin receptors. Of the five melanocortin receptors, MC2R and MC5R are expressed during adipocyte differentiation. AlphaMSH in addition to ACTH function as a regulator of inflammation by regulating cytokine production. [12]
        • melanocortin receptor 5
          in adipose_tissue
          • Function of melanocortins in regulating Il6 gene expression and production in adipocytes through membrane receptors which are called melanocortin receptors. Of the five melanocortin receptors, MC2R and MC5R are expressed during adipocyte differentiation. AlphaMSH in addition to ACTH function as a regulator of inflammation by regulating cytokine production. 2306 [12]
          • Melanocortins induce interleukin 6 gene expression and secretion through melanocortin receptor 2 and 5 in adipocytes. 2306 [12]
      • Anatomical structure: mast_cell

      • Anatomical structure: B-lymphocyte

      • Anatomical structure: T-lymphocyte

      • Anatomical structure: cell_of_endometrium_of_uterus

        • In humans, IL-6 is weakly expressed during the proliferative phase, but strong immunoreactivity is present during the mid-secretory phase, predominantly in the glandular and luminal epithelial cells. [13]

        Influenced by:

        • TGF-beta type II receptor
          in cell_of_endometrium_of_uterus
          • TGF-beta 1(from 10ex–12 to 10ex–8 M ), -beta 2 , -beta 3 and activin A(10ex–10 and 10ex–8 M ) reduces IL-6 release by the human endometrial epithelium. [14]
        • IL-1RI
          in cell_of_endometrium_of_uterus
          • Treatment with IL-1beta (10 <sup>–9</sup> M ) strongly stimulated LIF and IL-6 production. [14]
      • Anatomical structure: folliculostellate_cell

        Influenced by:

        • adenosine receptor 2B
          in folliculostellate_cell
          • Adenosine can stimulate IL-6 secretion in FS cells via the A2b receptor coupled principally to PLC/PKC and p38 MAPK. [15]
      • Anatomical structure: hematopoietic_stem_cell

        • Sex hormones suppress the synthesis and secretion of IL-6 by osteoblasts and bone marrow stem cells. [16]
      • Anatomical structure: osteoblast

        • Sex hormones suppress the synthesis and secretion of IL-6 by osteoblasts and bone marrow stem cells. [16]
        • IL-6 is a potent regulator for osteoclast differentiation and elicits bone resorption in in vivo and in vitro models that contain early osteoclast precursors. [17]
        • IL-6 and IL-11, synthesized in osteoblasts, are important stimulators of osteoclast development and physiologically regulate bone metabolism. [17]

        Influenced by:

        • PTHR1
          in osteoblast
          • Il-6 is produced by osteoblasts, and its production is stimulated by PTH and PGE2. [18]
        • EP3
          in osteoblast
          • Il-6 is produced by osteoblasts, and its production is stimulated by PTH and PGE2. [18]
        • EP4
          in osteoblast
          • Il-6 is produced by osteoblasts, and its production is stimulated by PTH and PGE2. [18]
        • IL-4Ralpha
          in osteoblast
          • Receptor-blocking antibodies to IL-4Ralpha inhibited the induction of IL-6 formation by both IL-4 and IL-13. IL-4 was tenfold more potent than IL-13 in inducing both alkaline phosphatase (ALP) activity and IL-6 secretion, whereas the cytokines were equipotent as inhibitors of cell proliferation. [19]
        • beta-2 adrenoreceptor
          in osteoblast
          • The maximum level of IL-6 production was over 40 pg/mL after 6 hr. The maximum level of IL-6 production was obtained at 10–100 &#x3bc;M epinephrine. [17]
        • bradykinin receptor B2
          in osteoblast
          • Bradykinin increased the synthesis of both IL-6 and PGE(2) and the increase in both was blocked by HOE140 (B2R antagonist). [20]
          • Bradykinin increased IL-6 and PGE2 synthesis via B2R but not B1R. [20]
      • Anatomical structure: osteoclast

      • Anatomical structure: Kupffer_cell_stellate_cell_of_liver

        • Human Kupffer cells activated with CEA, NCA and the peptide PELPK, express IL-1beta, TNF-alpha and IL-6. [21]
      • Anatomical structure: macrophage

      • Anatomical structure: monocyte

        Influenced by:

        • IL-4R type l
          in monocyte
          • IL-4 also inhibited IL-I0 and IL-6 production in all donors. [22]
        • IL-10R-alpha
          in monocyte
          • IL-10 inhibited IL-6 production in LPS-stimulated monocytes. [23]
      • Anatomical structure: dendritic_cell_in_lymphoid_tissues

      • Anatomical structure: epithelial_cell_with_microvilli

      • Anatomical structure: cervical_canal_of_uterus

      • Anatomical structure: bronchial_epithelial_cell

        Influenced by:

        • Sphingosine 1-phosphate receptor 1
          in lung
          • SP1 stimulates IL-6 prodcution in airway smooth muscle cells. [24]
      • Anatomical structure: propria_mucosa_of_bronchus

      • Anatomical structure: monocyte

      • Anatomical structure: B-lymphocyte

      • Anatomical structure: smooth_muscle_cell

        • Protein kinase C-mediated p38 mitogen activated protein kinase (MAPK) is responsible for IL-6 secretion. [25]
        • p38α is specifically responsible for LPA-induced IL-6 secretion. [25]
      • Anatomical structure: continuous_vascular_endothelial_cell_of_blood_vessels_and_lymphatics

        Influenced by:

        • Vascular endothelial growth factor receptor 1
          in continuous_vascular_endothelial_cell_of_blood_vessels_and_lymphatics
          • VEGF-stimulated interleukin-6 release from endothelium is selectively mediated through VEGFR1. [26]
      • Anatomical structure: placenta

      • Anatomical structure: chondrocyte

        • Chondrocytes are able to produce IL-6 and the IL-6 proteins secreted by chondrocytes were similar to those from fibroblasts. [27]

        Influenced by:

        • CMKLR1
          in chondrocyte
          • The results show an increased concentration of IL-6 as a result of chemerin stimulation in comparison to unstimulated control cells [28]
      • Anatomical structure: fibroblast

        • Fibroblast secretion of biologically active IL-6 has been reported in response to stimulation with both TNFa and IL-lalpha. [29]

      Targets

      CellIGF-2RIL-6R
      adrenal cortex Present
      cell of adrenal gland zona fasciculata Present
      Influences
      • corticosterone
      • cortisol
      • cortisone
      cell of adrenal gland zona glomerulosa Present
      cell of adrenal gland zona reticularis Present
      Influences
      • dehydro-3-epiandrosterone
      • androstenedione
      • testosterone
      cell of endometrium of uterus Present
      dendritic cell in lymphoid tissues follicular Present
      epithelial cell with microvilli Present
      Influences
      • fibrinogen
      hepatocyte Present
      Influences
      • hepcidin
      • SAA1
      • fibrinogen
      monocyte Present
      parathyroid gland Present
      Influences
      • PTH
      Reference