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Gene Review

Lif  -  leukemia inhibitory factor

Rattus norvegicus

Synonyms: Cholinergic neuronal differentiation factor, LIF, Leukemia inhibitory factor
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Disease relevance of Lif


Psychiatry related information on Lif

  • The LIF-treated rats displayed decreased motor activity during juvenile stages, and developed abnormal prepulse inhibition in the acoustic startle test during and after adolescence [5].

High impact information on Lif


Chemical compound and disease context of Lif


Biological context of Lif

  • The dendritic retraction induced by LIF exhibited substantial specificity because it was not accompanied by changes in cell number, in the rate of axonal growth, or in the expression of axonal cytoskeletal elements [12].
  • In contrast, less than 10% of newborn NG neurons survived in the presence of LIF or CNTF, suggesting a loss in responsiveness to these factors during fetal development in vivo [13].
  • Expression of leukemia inhibitory factor (LIF)/interleukin-6 family cytokines and receptors during in vitro osteogenesis: differential regulation by dexamethasone and LIF [14].
  • After seizure, IL-6, LIF, and IL-11 exhibited a rapid, robust, and transient upregulation in non-principal cells [15].
  • LIF signaling is responsible for cortical precursor cell survival [16].

Anatomical context of Lif

  • 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 [12].
  • Leukemia inhibitory factor and neurotrophins support overlapping populations of rat nodose sensory neurons in culture [13].
  • To determine whether development of NGF-independent sensory neurons could be similarly regulated, the present study examined the effects of LIF and the related cytokine-like growth factor, ciliary neurotrophic factor (CNTF), on survival of rat nodose ganglion (NG) cells in culture [13].
  • Previously, we reported that LIF inhibits, in a non-IL-6-dependent manner, osteoblast differentiation and bone nodule formation in the rat calvaria (RC) model, an effect that is antagonized by dexamethasone (Dex) [14].
  • LIF also exhibited a remarkably early and transient induction in the granule cell layer of the dentate gyrus [15].

Associations of Lif with chemical compounds


Regulatory relationships of Lif


Other interactions of Lif

  • 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 [13].
  • In TGR, the increased level of LIF was accompanied by a decrease in mRNA levels for LIFR and CNTFR [26].
  • The protein levels of IL-6, LIF and CT-1 were investigated by western blot [26].
  • In vitro, CNTF and LIF induced in crest-derived cells nuclear translocation of STAT3 (signal transducer and activator of transcription 3), a concentration-dependent increase in expression of neuronal or glial markers, and a decrease in expression of the precursor marker, nestin [27].
  • Early induction of phosphorylated Stat3 was significantly detected on the ischemic side in the high-LIF group after LIF injection [4].

Analytical, diagnostic and therapeutic context of Lif

  • These data indicate that multiple members of the LIF/IL-6 family and their receptors are expressed in RC cell cultures, and are differentially regulated by Dex and LIF, suggesting that these cytokines play a complex and interdependent role, further modulated by glucocorticoid levels, in osteoprogenitor differentiation and bone nodule formation [14].
  • Real-time PCR analysis revealed that LIF mRNA expression was significantly increased from day 1 to day 7 after reperfusion and that LIFR mRNA was upregulated from day 4 to day 14 [3].
  • It is likely that increased LIF expression following peripheral axotomy plays an important role in the novel sympathetic sprouting observed within sensory ganglia following peripheral nerve injury [28].
  • Growing or growth-arrested rat mesangial cells constitutively expressed very low levels of LIF mRNA, barely detectable by Northern blot analysis [29].
  • 2. Immunocytochemistry was used to study the distribution and density of tyrosine hydroxylase-immunoreactive (TH-IR) fibres within the lumbar dorsal root ganglia and lumbar spinal nerves 14 days following continuous intrathecal infusion of LIF (0.33 mg ml-1), or 14 days following unilateral peripheral nerve axotomy [28].


  1. DNA methylation controls the responsiveness of hepatoma cells to leukemia inhibitory factor. Blanchard, F., Tracy, E., Smith, J., Chattopadhyay, S., Wang, Y., Held, W.A., Baumann, H. Hepatology (2003) [Pubmed]
  2. 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]
  3. Leukemia inhibitory factor is involved in tubular regeneration after experimental acute renal failure. Yoshino, J., Monkawa, T., Tsuji, M., Hayashi, M., Saruta, T. J. Am. Soc. Nephrol. (2003) [Pubmed]
  4. Activation of cytokine signaling through leukemia inhibitory factor receptor (LIFR)/gp130 attenuates ischemic brain injury in rats. Suzuki, S., Yamashita, T., Tanaka, K., Hattori, H., Sawamoto, K., Okano, H., Suzuki, N. J. Cereb. Blood Flow Metab. (2005) [Pubmed]
  5. Neonatal impact of leukemia inhibitory factor on neurobehavioral development in rats. Watanabe, Y., Hashimoto, S., Kakita, A., Takahashi, H., Ko, J., Mizuno, M., Someya, T., Patterson, P.H., Nawa, H. Neurosci. Res. (2004) [Pubmed]
  6. Leukemia inhibitory factor (LIF) stimulates proopiomelanocortin (POMC) expression in a corticotroph cell line. Role of STAT pathway. Ray, D.W., Ren, S.G., Melmed, S. J. Clin. Invest. (1996) [Pubmed]
  7. Postnatal development of survival responsiveness in rat sympathetic neurons to leukemia inhibitory factor and ciliary neurotrophic factor. Kotzbauer, P.T., Lampe, P.A., Estus, S., Milbrandt, J., Johnson, E.M. Neuron (1994) [Pubmed]
  8. Retrograde axonal transport of LIF is increased by peripheral nerve injury: correlation with increased LIF expression in distal nerve. Curtis, R., Scherer, S.S., Somogyi, R., Adryan, K.M., Ip, N.Y., Zhu, Y., Lindsay, R.M., DiStefano, P.S. Neuron (1994) [Pubmed]
  9. 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]
  10. Leukemia inhibitory factor regulates prolactin secretion in prolactinoma and lactotroph cells. Ben-Shlomo, A., Miklovsky, I., Ren, S.G., Yong, W.H., Heaney, A.P., Culler, M.D., Melmed, S. J. Clin. Endocrinol. Metab. (2003) [Pubmed]
  11. Differential expression of M-CSF, LIF, and TNF-alpha genes in normal and malignant rat glial cells: regulation by lipopolysaccharide and vitamin D. Furman, I., Baudet, C., Brachet, P. J. Neurosci. Res. (1996) [Pubmed]
  12. 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]
  13. 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]
  14. Expression of leukemia inhibitory factor (LIF)/interleukin-6 family cytokines and receptors during in vitro osteogenesis: differential regulation by dexamethasone and LIF. Liu, F., Aubin, J.E., Malaval, L. Bone (2002) [Pubmed]
  15. Spatiotemporal distribution of gp130 cytokines and their receptors after status epilepticus: comparison with neuronal degeneration and microglial activation. Rosell, D.R., Nacher, J., Akama, K.T., McEwen, B.S. Neuroscience (2003) [Pubmed]
  16. Developmental stage-dependent self-regulation of embryonic cortical precursor cell survival and differentiation by leukemia inhibitory factor. Chang, M.Y., Park, C.H., Son, H., Lee, Y.S., Lee, S.H. Cell Death Differ. (2004) [Pubmed]
  17. mRNAs encoding muscarinic and substance P receptors in cultured sympathetic neurons are differentially regulated by LIF or CNTF. Ludlam, W.H., Zang, Z., McCarson, K.E., Krause, J.E., Spray, D.C., Kessler, J.A. Dev. Biol. (1994) [Pubmed]
  18. Leukemia inhibitory factor and ciliary neurotrophic factor increase activated Ras in a neuroblastoma cell line and in sympathetic neuron cultures. Schwarzschild, M.A., Dauer, W.T., Lewis, S.E., Hamill, L.K., Fink, J.S., Hyman, S.E. J. Neurochem. (1994) [Pubmed]
  19. Expression of leukemia inhibitory factor and its receptor during liver regeneration in the adult rat. Omori, N., Evarts, R.P., Omori, M., Hu, Z., Marsden, E.R., Thorgeirsson, S.S. Lab. Invest. (1996) [Pubmed]
  20. Kainic acid induces leukemia inhibitory factor mRNA expression in the rat brain: differences in the time course of mRNA expression between the dentate gyrus and hippocampal CA1/CA3 subfields. Minami, M., Maekawa, K., Yamakuni, H., Katayama, T., Nakamura, J., Satoh, M. Brain Res. Mol. Brain Res. (2002) [Pubmed]
  21. Leukemia inhibitory factor activates cardiac L-Type Ca2+ channels via phosphorylation of serine 1829 in the rabbit Cav1.2 subunit. Takahashi, E., Fukuda, K., Miyoshi, S., Murata, M., Kato, T., Ita, M., Tanabe, T., Ogawa, S. Circ. Res. (2004) [Pubmed]
  22. LIF, but not IL-6, regulates osteoprogenitor differentiation in rat calvaria cell cultures: modulation by dexamethasone. Malaval, L., Gupta, A.K., Liu, F., Delmas, P.D., Aubin, J.E. J. Bone Miner. Res. (1998) [Pubmed]
  23. Cytokine G-protein signaling crosstalk in cardiomyocytes: attenuation of Jak-STAT activation by endothelin-1. Booz, G.W., Day, J.N., Speth, R., Baker, K.M. Mol. Cell. Biochem. (2002) [Pubmed]
  24. Activation of JAK-STAT and MAP kinases by leukemia inhibitory factor through gp130 in cardiac myocytes. Kunisada, K., Hirota, H., Fujio, Y., Matsui, H., Tani, Y., Yamauchi-Takihara, K., Kishimoto, T. Circulation (1996) [Pubmed]
  25. Glycoprotein 130 regulates cardiac myocyte survival in doxorubicin-induced apoptosis through phosphatidylinositol 3-kinase/Akt phosphorylation and Bcl-xL/caspase-3 interaction. Negoro, S., Oh, H., Tone, E., Kunisada, K., Fujio, Y., Walsh, K., Kishimoto, T., Yamauchi-Takihara, K. Circulation (2001) [Pubmed]
  26. Increased expression of IL-6 and LIF in the hypertrophied left ventricle of TGR(mRen2)27 and SHR rats. Kurdi, M., Randon, J., Cerutti, C., Bricca, G. Mol. Cell. Biochem. (2005) [Pubmed]
  27. Promotion of the development of enteric neurons and glia by neuropoietic cytokines: interactions with neurotrophin-3. Chalazonitis, A., Rothman, T.P., Chen, J., Vinson, E.N., MacLennan, A.J., Gershon, M.D. Dev. Biol. (1998) [Pubmed]
  28. Leukemia inhibitory factor induces sympathetic sprouting in intact dorsal root ganglia in the adult rat in vivo. Thompson, S.W., Majithia, A.A. J. Physiol. (Lond.) (1998) [Pubmed]
  29. Cytokine-induced expression of leukemia inhibitory factor in renal mesangial cells. Hartner, A., Sterzel, R.B., Reindl, N., Hocke, G.M., Fey, G.H., Goppelt-Struebe, M. Kidney Int. (1994) [Pubmed]
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