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Gene Review

Cntf  -  ciliary neurotrophic factor

Rattus norvegicus

Synonyms: CNTF, Ciliary neurotrophic factor
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Disease relevance of Cntf

  • Soluble footpad extracts induced the same changes in NBFL neuroblastoma cells as LIF and CNTF, including increased vasoactive intestinal peptide mRNA, STAT3 dimerization, and DNA binding, and stimulation of transcription from the vasoactive intestinal peptide cytokine-responsive element [1].
  • We hypothesize that CNTF released from destroyed beta-cells during the inflammatory islet lesion leading to IDDM may potentiate IL-1beta action on the beta-cells [2].
  • IL-6 is related to ciliary neurotrophic factor (CNTF), a trophic factor for motoneurons, sensory dorsal root ganglion (DRG) neurons, and other neuronal subpopulations [3].
  • CNTF expression was up-regulated from the day following ICH induction and reached a peak level at 5 to 14 days, with increased expression observed in brain tissue surrounding the hematoma lesion and white matter structures in association with astroglial proliferation [4].
  • However, little is known about the expression of CNTF or that of its receptor (CNTFR-alpha) in cases of intracerebral hemorrhage (ICH) [4].

Psychiatry related information on Cntf


High impact information on Cntf

  • Trophic effect of ciliary neurotrophic factor on denervated skeletal muscle [7].
  • In vivo, administration of CNTF activates these receptors on skeletal muscle by inducing receptor phosphorylation and immediate-early gene responses [7].
  • Adenoviral gene transfer of ciliary neurotrophic factor and brain-derived neurotrophic factor leads to long-term survival of axotomized motor neurons [8].
  • The neurotrophic factors ciliary neurotrophic factor and brain-derived neurotrophic factor can prevent motor neuron cell death during development and after nerve lesion in neonatal rodents [8].
  • Although CNTF is abundant in adult sciatic nerve, the mature protein lacks a signal sequence and is not secreted; therefore, it has been proposed to act as a lesion factor [9].

Chemical compound and disease context of Cntf


Biological context of Cntf


Anatomical context of Cntf

  • These findings strongly suggest that increases in endogenous bFGF and/or CNTF play key roles in injury-induced photoreceptor rescue [18].
  • Our data indicate that leukemia inhibitory factor (LIF) and ciliary neurotrophic factor (CNTF) cause sympathetic neurons to retract their dendrites in vitro, ultimately leading to an approximately 80% reduction in the size of the arbor [19].
  • In addition, CNTFR3alpha inhibits the proliferation of the TF1 hematopoietic cell line triggered by CNTF plus soluble wild type CNTFRalpha but not by IL-6 or oncostatin M [20].
  • Ciliary neurotrophic factor potentiates the beta-cell inhibitory effect of IL-1beta in rat pancreatic islets associated with increased nitric oxide synthesis and increased expression of inducible nitric oxide synthase [2].
  • In conclusion, CNTF is constitutively expressed in pancreatic beta-cells and potentiates the beta-cell inhibitory effect of IL-1beta in association with increased iNOS expression and NO synthesis, an effect shared by IL-6 but not by beta-NGF [2].

Associations of Cntf with chemical compounds

  • CNTF (20 ng/ml) potentiated IL-1beta-mediated (5-150 pg/ml) nitric oxide (NO) synthesis from neonatal Wistar rat islets by 31-116%, inhibition of accumulated insulin release by 34-49%, and inhibition insulin response to a 2-h glucose challenge by 31-36% [2].
  • Positions 268 and 269 of CNTFRalpha appear to be critical for its interaction with gp130 and LIFRbeta, whereby alanine substitution of the residues at these positions results in antagonism of the CNTF-induced response [20].
  • Retinoic acid downregulates the expression of ciliary neurotrophic factor in rat Schwann cells [21].
  • In vivo, the neuroprotective activity of CNTF in constant-light conditions was attenuated by 10 microg/eye LY294002 (Dunnet's test, p < 0.05) [22].
  • Implantation of C6 lines expressing a nonsecreted form of CNTF, or the parental C6 line itself, did not result in wasting effects [10].

Physical interactions of Cntf


Co-localisations of Cntf


Regulatory relationships of Cntf


Other interactions of Cntf

  • IL-6 (10 ng/ml) also potentiated IL-1beta-mediated NO synthesis and inhibition of insulin release, whereas beta-nerve growth factor (NGF) (5 or 50 ng/ml) had no effect. mRNA for CNTF was expressed in rat islets and in islet cell lines [2].
  • Treatment of dissociate cultures of Embryonic Day (E) 16.5 NG with LIF or CNTF (10 ng/ml) resulted in a four- to fivefold increase in neuronal survival; the number of neurons supported by either factor represented approximately 50% of the total NG population [17].
  • Expression of CNTF/LIF-receptor components and activation of STAT3 signaling in axotomized facial motoneurons: evidence for a sequential postlesional function of the cytokines [31].
  • Our novel findings of increased cardiac CNTF and cardiopulmonary MCP-1 mRNA indicate a role for these factors in the pathogenesis of HF [32].
  • Expression of CNTF and GFAP mRNAs followed a time course similar to that of bFGF [33].

Analytical, diagnostic and therapeutic context of Cntf


  1. A sweat gland-derived differentiation activity acts through known cytokine signaling pathways. Habecker, B.A., Symes, A.J., Stahl, N., Francis, N.J., Economides, A., Fink, J.S., Yancopoulos, G.D., Landis, S.C. J. Biol. Chem. (1997) [Pubmed]
  2. Ciliary neurotrophic factor potentiates the beta-cell inhibitory effect of IL-1beta in rat pancreatic islets associated with increased nitric oxide synthesis and increased expression of inducible nitric oxide synthase. Wadt, K.A., Larsen, C.M., Andersen, H.U., Nielsen, K., Karlsen, A.E., Mandrup-Poulsen, T. Diabetes (1998) [Pubmed]
  3. Interleukin-6 (IL-6) and its soluble receptor support survival of sensory neurons. Thier, M., März, P., Otten, U., Weis, J., Rose-John, S. J. Neurosci. Res. (1999) [Pubmed]
  4. Expression of ciliary neurotrophic factor (CNTF), CNTF receptor alpha (CNTFR-alpha) following experimental intracerebral hemorrhage in rats. Yokota, H., Yoshikawa, M., Hirabayashi, H., Nakase, H., Uranishi, R., Nishimura, F., Sugie, Y., Ishizaka, S., Sakaki, T. Neurosci. Lett. (2005) [Pubmed]
  5. Neuroprotective effect of interleukin-6 and IL6/IL6R chimera in the quinolinic acid rat model of Huntington's syndrome. Bensadoun, J.C., de Almeida, L.P., Dréano, M., Aebischer, P., Déglon, N. Eur. J. Neurosci. (2001) [Pubmed]
  6. Ciliary neurotrophic factor attenuates spatial cognition impairment, cortical infarction and thalamic degeneration in spontaneously hypertensive rats with focal cerebral ischemia. Kumon, Y., Sakaki, S., Watanabe, H., Nakano, K., Ohta, S., Matsuda, S., Yoshimura, H., Sakanaka, M. Neurosci. Lett. (1996) [Pubmed]
  7. Trophic effect of ciliary neurotrophic factor on denervated skeletal muscle. Helgren, M.E., Squinto, S.P., Davis, H.L., Parry, D.J., Boulton, T.G., Heck, C.S., Zhu, Y., Yancopoulos, G.D., Lindsay, R.M., DiStefano, P.S. Cell (1994) [Pubmed]
  8. Adenoviral gene transfer of ciliary neurotrophic factor and brain-derived neurotrophic factor leads to long-term survival of axotomized motor neurons. Gravel, C., Götz, R., Lorrain, A., Sendtner, M. Nat. Med. (1997) [Pubmed]
  9. Retrograde axonal transport of ciliary neurotrophic factor is increased by peripheral nerve injury. Curtis, R., Adryan, K.M., Zhu, Y., Harkness, P.J., Lindsay, R.M., DiStefano, P.S. Nature (1993) [Pubmed]
  10. Systemic administration of ciliary neurotrophic factor induces cachexia in rodents. Henderson, J.T., Seniuk, N.A., Richardson, P.M., Gauldie, J., Roder, J.C. J. Clin. Invest. (1994) [Pubmed]
  11. Coordinate regulation of STAT signaling and c-fos expression by the tyrosine phosphatase SHP-2. Servidei, T., Aoki, Y., Lewis, S.E., Symes, A., Fink, J.S., Reeves, S.A. J. Biol. Chem. (1998) [Pubmed]
  12. LIF and CNTF, which share the gp130 transduction system, stimulate hepatic lipid metabolism in rats. Nonogaki, K., Pan, X.M., Moser, A.H., Shigenaga, J., Staprans, I., Sakamoto, N., Grunfeld, C., Feingold, K.R. Am. J. Physiol. (1996) [Pubmed]
  13. Corticostriatopallidal neuroprotection by adenovirus-mediated ciliary neurotrophic factor gene transfer in a rat model of progressive striatal degeneration. Mittoux, V., Ouary, S., Monville, C., Lisovoski, F., Poyot, T., Conde, F., Escartin, C., Robichon, R., Brouillet, E., Peschanski, M., Hantraye, P. J. Neurosci. (2002) [Pubmed]
  14. Changes in neurotrophic factor expression and receptor activation following exposure of hippocampal neuron/astrocyte cocultures to kainic acid. Rudge, J.S., Pasnikowski, E.M., Holst, P., Lindsay, R.M. J. Neurosci. (1995) [Pubmed]
  15. Cardiotrophin-1 displays early expression in the murine heart tube and promotes cardiac myocyte survival. Sheng, Z., Pennica, D., Wood, W.I., Chien, K.R. Development (1996) [Pubmed]
  16. CNTF induces raphe neuronal precursors to switch from a serotonergic to a cholinergic phenotype in vitro. Rudge, J.S., Eaton, M.J., Mather, P., Lindsay, R.M., Whittemore, S.R. Mol. Cell. Neurosci. (1996) [Pubmed]
  17. Leukemia inhibitory factor and neurotrophins support overlapping populations of rat nodose sensory neurons in culture. Thaler, C.D., Suhr, L., Ip, N., Katz, D.M. Dev. Biol. (1994) [Pubmed]
  18. Injury-induced upregulation of bFGF and CNTF mRNAS in the rat retina. Wen, R., Song, Y., Cheng, T., Matthes, M.T., Yasumura, D., LaVail, M.M., Steinberg, R.H. J. Neurosci. (1995) [Pubmed]
  19. Leukemia inhibitory factor and ciliary neurotrophic factor cause dendritic retraction in cultured rat sympathetic neurons. Guo, X., Chandrasekaran, V., Lein, P., Kaplan, P.L., Higgins, D. J. Neurosci. (1999) [Pubmed]
  20. Alanine substitution for Thr268 and Asp269 of soluble ciliary neurotrophic factor (CNTF) receptor alpha component defines a specific antagonist for the CNTF response. Auguste, P., Robledo, O., Olivier, C., Froger, J., Praloran, V., Pouplard-Barthelaix, A., Gascan, H. J. Biol. Chem. (1996) [Pubmed]
  21. Retinoic acid downregulates the expression of ciliary neurotrophic factor in rat Schwann cells. Johann, V., Jeliaznik, N., Schrage, K., Mey, J. Neurosci. Lett. (2003) [Pubmed]
  22. Ciliary neurotrophic factor protects rat retina cells in vitro and in vivo via PI3 kinase. Ikeda, K., Tatsuno, T., Noguchi, H., Nakayama, C. Curr. Eye Res. (2004) [Pubmed]
  23. Ciliary neurotrophic factor regulates fibrinogen gene expression in hepatocytes by binding to the interleukin-6 receptor. Nesbitt, J.E., Fuentes, N.L., Fuller, G.M. Biochem. Biophys. Res. Commun. (1993) [Pubmed]
  24. Interleukin-6 and ciliary neurotrophic factor trigger janus kinase activation and early gene response in rat hepatocytes. Wang, Y., Fuller, G.M. Gene (1995) [Pubmed]
  25. Expression of ciliary neurotrophic factor receptor-alpha messenger RNA in neonatal and adult rat brain: an in situ hybridization study. Lee, M.Y., Hofmann, H.D., Kirsch, M. Neuroscience (1997) [Pubmed]
  26. Astroglial ciliary neurotrophic factor mRNA expression is increased in fields of axonal sprouting in deafferented hippocampus. Guthrie, K.M., Woods, A.G., Nguyen, T., Gall, C.M. J. Comp. Neurol. (1997) [Pubmed]
  27. IL-6 up-regulates CNTF mRNA expression and enhances neurite regeneration. Shuto, T., Horie, H., Hikawa, N., Sango, K., Tokashiki, A., Murata, H., Yamamoto, I., Ishikawa, Y. Neuroreport (2001) [Pubmed]
  28. Synergistic effects of brain-derived neurotrophic factor and ciliary neurotrophic factor on cultured basal forebrain cholinergic neurons from postnatal 2-week-old rats. Hashimoto, Y., Abiru, Y., Nishio, C., Hatanaka, H. Brain Res. Dev. Brain Res. (1999) [Pubmed]
  29. Hepatocyte growth factor promotes motor neuron survival and synergizes with ciliary neurotrophic factor. Wong, V., Glass, D.J., Arriaga, R., Yancopoulos, G.D., Lindsay, R.M., Conn, G. J. Biol. Chem. (1997) [Pubmed]
  30. Injury-induced regulation of ciliary neurotrophic factor mRNA in the adult rat brain. Ip, N.Y., Wiegand, S.J., Morse, J., Rudge, J.S. Eur. J. Neurosci. (1993) [Pubmed]
  31. Expression of CNTF/LIF-receptor components and activation of STAT3 signaling in axotomized facial motoneurons: evidence for a sequential postlesional function of the cytokines. Haas, C.A., Hofmann, H.D., Kirsch, M. J. Neurobiol. (1999) [Pubmed]
  32. Cardiopulmonary alterations in mRNA expression for interleukin-1beta, the interleukin-6 superfamily and CXC-chemokines during development of postischaemic heart failure in the rat. Tønnessen, T., Florholmen, G., Henriksen, U.L., Christensen, G. Clinical physiology and functional imaging. (2003) [Pubmed]
  33. Development of normal and injury-induced gene expression of aFGF, bFGF, CNTF, BDNF, GFAP and IGF-I in the rat retina. Cao, W., Li, F., Steinberg, R.H., Lavail, M.M. Exp. Eye Res. (2001) [Pubmed]
  34. Cardiotrophin-1 induces the same neuropeptides in sympathetic neurons as do neuropoietic cytokines. Cheng, J.G., Pennica, D., Patterson, P.H. J. Neurochem. (1997) [Pubmed]
  35. Differential regulation of ciliary neurotrophic factor (CNTF) and CNTF receptor alpha expression in astrocytes and neurons of the fascia dentata after entorhinal cortex lesion. Lee, M.Y., Deller, T., Kirsch, M., Frotscher, M., Hofmann, H.D. J. Neurosci. (1997) [Pubmed]
  36. Upregulation of ciliary neurotrophic factor (CNTF) and CNTF receptor alpha in rat kidney with ischemia-reperfusion injury. Yang, C.W., Lim, S.W., Han, K.W., Ahn, H.J., Park, J.H., Kim, Y.H., Kirsh, M., Cha, J.H., Park, J.H., Kim, Y.S., Kim, J., Bang, B.K. J. Am. Soc. Nephrol. (2001) [Pubmed]
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