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Cited by 478Cytokine Signaling Pathways and InteractionsPluripotent Stem Cells ResearchGrowth Hormone and Insulin-like Growth Factors

Leukemia inhibitory factor (LIF)

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Nicola, Nicos A., Babon, Jeffrey J.·2015·Cytokine & Growth Factor Reviews
DOI 10.1016/j.cytogfr.2015.07.001PMC PMC4581962
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Abstract

Leukemia inhibitory factor (LIF) is the most pleiotropic member of the interleukin-6 family of cytokines. It utilises a receptor that consists of the LIF receptor β and gp130 and this receptor complex is also used by ciliary neurotrophic growth factor (CNTF), oncostatin M, cardiotrophin1 (CT1) and cardiotrophin-like cytokine (CLC). Despite common signal transduction mechanisms (JAK/STAT, MAPK and PI3K) LIF can have paradoxically opposite effects in different cell types including stimulating or inhibiting each of cell proliferation, differentiation and survival. While LIF can act on a wide range of cell types, LIF knockout mice have revealed that many of these actions are not apparent during ordinary development and that they may be the result of induced LIF expression during tissue damage or injury. Nevertheless LIF does appear to have non-redundant actions in maternal receptivity to blastocyst implantation, placental formation and in the development of the nervous system. LIF has also found practical use in the maintenance of self-renewal and totipotency of embryonic stem cells and induced pluripotent stem cells.

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Crossref · 10.1016/j.cytogfr.2015.07.001

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  • There is an overall reduced level of LIF in THS-exposed mouse wounds.

    “Furthermore, we show that there is an overall reduced level of the interleukin 6 class protein LIF; this cytokine is critical for monocyte maturation into macrophage and for proper formation of the granulation tissue [64].”

    From Tobacco toxins deposited on surfaces (third hand smoke) impair wound healing (2016) · cites this paper as [64]

    The paper identifies LIF as an interleukin-6-family cytokine, but its ‘The hemopoietic system’ and ‘Summary and outlook’ sections do not establish that LIF is critical for monocyte-to-macrophage maturation or granulation-tissue formation; the summary says LIF has few effects on myeloid cells. The reduced LIF level in THS-exposed wounds is presented as the citing authors’ own finding (‘we show’), not as a finding attributed to this source. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

  • LIF is critical for monocyte maturation into macrophage and for proper formation of granulation tissue.

    “Furthermore, we show that there is an overall reduced level of the interleukin 6 class protein LIF; this cytokine is critical for monocyte maturation into macrophage and for proper formation of the granulation tissue [64].”

    From Tobacco toxins deposited on surfaces (third hand smoke) impair wound healing (2016) · cites this paper as [64]

    The hemopoietic-system section discusses LIF’s limited effects on blood-forming cells but does not address monocyte maturation into macrophages. The neuromuscular-system section describes muscle regeneration after injury, not granulation-tissue formation. Searches for monocyte-to-macrophage maturation and granulation tissue found no passage supporting either attributed role. (LLM, conf=0.73)

    Experimental — accuracy not yet measured

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  1. [1]Gearing DP Gough NM King JA Hilton DJ Nicola NA Simpson RJ Molecular cloning and expression of cDNA encoding a murine myeloid leukaemia inhibitory factor (LIF) The EMBO journal 1987 6 3995 4002 3127201 PMC553879
  2. [2]Smith AG Heath JK Donaldson DD Wong GG Moreau J Stahl M Inhibition of pluripotential embryonic stem cell differentiation by purified polypeptides Nature 1988 336 688 90 3143917
  3. [3]Moreau JF Bonneville M Godard A Gascan H Gruart V Moore MA Characterization of a factor produced by human T cell clones exhibiting eosinophil-activating and burst-promoting activities Journal of immunology 1987 138 3844 9 3295040
  4. [4]Baumann H Onorato V Gauldie J Jahreis GP Distinct sets of acute phase plasma proteins are stimulated by separate human hepatocyte-stimulating factors and monokines in rat hepatoma cells The Journal of biological chemistry 1987 262 9756 68 2439511
  5. [5]Patterson PH Chun LL The induction of acetylcholine synthesis in primary cultures of dissociated rat sympathetic neurons. I. Effects of conditioned medium Developmental biology 1977 56 263 80 557424
  6. [6]Patterson PH Chun LL The induction of acetylcholine synthesis in primary cultures of dissociated rat sympathetic neurons. II. Developmental aspects Developmental biology 1977 60 473 81 562803
  7. [7]Mori M Yamaguchi K Abe K Purification of a lipoprotein lipase-inhibiting protein produced by a melanoma cell line associated with cancer cachexia Biochemical and biophysical research communications 1989 160 1085 92 2730639
  8. [8]Robinson RC Grey LM Staunton D Vankelecom H Vernallis AB Moreau JF The crystal structure and biological function of leukemia inhibitory factor: implications for receptor binding Cell 1994 77 1101 16 8020098
  9. [9]Hinds MG Maurer T Zhang JG Nicola NA Norton RS Solution structure of leukemia inhibitory factor The Journal of biological chemistry 1998 273 13738 45 9593715
  10. [10]Boulanger MJ Bankovich AJ Kortemme T Baker D Garcia KC Convergent mechanisms for recognition of divergent cytokines by the shared signaling receptor gp130 Molecular cell 2003 12 577 89 14527405
  11. [11]Gearing DP Comeau MR Friend DJ Gimpel SD Thut CJ McGourty J The IL-6 signal transducer, gp130: an oncostatin M receptor and affinity converter for the LIF receptor Science 1992 255 1434 7 1542794
  12. [12]Boulanger MJ Chow DC Brevnova EE Garcia KC Hexameric structure and assembly of the interleukin-6/IL-6 alpha-receptor/gp130 complex Science 2003 300 2101 4 12829785
  13. [13]Chow D Ho J Nguyen Pham TL Rose-John S Garcia KC In vitro reconstitution of recognition and activation complexes between interleukin-6 and gp130 Biochemistry 2001 40 7593 603 11412113
  14. [14]Matadeen R Hon WC Heath JK Jones EY Fuller S The dynamics of signal triggering in a gp130-receptor complex Structure 2007 15 441 8 17437716 PMC1885967
  15. [15]Skiniotis G Lupardus PJ Martick M Walz T Garcia KC Structural organization of a full-length gp130/LIF-R cytokine receptor transmembrane complex Molecular cell 2008 31 737 48 18775332 PMC2607196
  16. [16]Gearing DP Thut CJ VandeBos T Gimpel SD Delaney PB King J Leukemia inhibitory factor receptor is structurally related to the IL-6 signal transducer, gp130 The EMBO journal 1991 10 2839 48 1915266 PMC452994
  17. [17]Xu Y Kershaw NJ Luo CS Soo P Pocock MJ Czabotar PE Crystal structure of the entire ectodomain of gp130: insights into the molecular assembly of the tall cytokine receptor complexes The Journal of biological chemistry 2010 285 21214 8 20489211 PMC2898449
  18. [18]Stahl N Boulton TG Farruggella T Ip NY Davis S Witthuhn BA Association and activation of Jak-Tyk kinases by CNTF-LIF-OSM-IL-6 beta receptor components Science 1994 263 92 5 8272873
  19. [19]Huyton T Zhang JG Luo CS Lou MZ Hilton DJ Nicola NA An unusual cytokine:Ig-domain interaction revealed in the crystal structure of leukemia inhibitory factor (LIF) in complex with the LIF receptor Proceedings of the National Academy of Sciences of the United States of America 2007 104 12737 42 17652170 PMC1937536
  20. [20]Boulanger MJ Garcia KC Shared cytokine signaling receptors: structural insights from the gp130 system Advances in protein chemistry 2004 68 107 46 15500860
  21. [21]Hilton DJ Nicola NA Metcalf D Distribution and comparison of receptors for leukemia inhibitory factor on murine hemopoietic and hepatic cells Journal of cellular physiology 1991 146 207 15 1900303
  22. [22]Hilton DJ Nicola NA Kinetic analyses of the binding of leukemia inhibitory factor to receptor on cells and membranes and in detergent solution The Journal of biological chemistry 1992 267 10238 47 1587813
  23. [23]Lupardus PJ Skiniotis G Rice AJ Thomas C Fischer S Walz T Structural snapshots of full-length Jak1, a transmembrane gp130/IL-6/IL-6Ralpha cytokine receptor complex, and the receptor-Jak1 holocomplex Structure 2011 19 45 55 21220115 PMC3052743
  24. [24]Gouin F Couillaud S Cottrel M Godard A Passuti N Heymann D Presence of leukaemia inhibitory factor (LIF) and LIF-receptor chain (gp190) in osteoclast-like cells cultured from human giant cell tumour of bone. Ultrastructural distribution Cytokine 1999 11 282 9 10328867
  25. [25]Ni H Ding NZ Harper MJ Yang ZM Expression of leukemia inhibitory factor receptor and gp130 in mouse uterus during early pregnancy Molecular reproduction and development 2002 63 143 50 12203823
  26. [26]Scott RL Gurusinghe AD Rudvosky AA Kozlakivsky V Murray SS Satoh M Expression of leukemia inhibitory factor receptor mRNA in sensory dorsal root ganglion and spinal motor neurons of the neonatal rat Neuroscience letters 2000 295 49 53 11078934
  27. [27]Williams RL Hilton DJ Pease S Willson TA Stewart CL Gearing DP Myeloid leukaemia inhibitory factor maintains the developmental potential of embryonic stem cells Nature 1988 336 684 7 3143916
  28. [28]Wilks AF Two putative protein-tyrosine kinases identified by application of the polymerase chain reaction Proceedings of the National Academy of Sciences of the United States of America 1989 86 1603 7 2466296 PMC286746
  29. [29]Rodig SJ Meraz MA White JM Lampe PA Riley JK Arthur CD Disruption of the Jak1 gene demonstrates obligatory and nonredundant roles of the Jaks in cytokine-induced biologic responses Cell 1998 93 373 83 9590172
  30. [30]Chung BM Kang HC Han SY Heo HS Lee JJ Jeon J Jak2 and Tyk2 are necessary for lineage-specific differentiation, but not for the maintenance of self-renewal of mouse embryonic stem cells Biochemical and biophysical research communications 2006 351 682 8 17078929
  31. [31]Takahashi Y Takahashi M Carpino N Jou ST Chao JR Tanaka S Leukemia inhibitory factor regulates trophoblast giant cell differentiation via Janus kinase 1-signal transducer and activator of transcription 3-suppressor of cytokine signaling 3 pathway Molecular endocrinology 2008 22 1673 81 18451094 PMC5419438
  32. [32]Ernst M Oates A Dunn AR Gp130-mediated signal transduction in embryonic stem cells involves activation of Jak and Ras/mitogen-activated protein kinase pathways The Journal of biological chemistry 1996 271 30136 43 8939963
  33. [33]Williams NK Bamert RS Patel O Wang C Walden PM Wilks AF Dissecting specificity in the Janus kinases: the structures of JAK-specific inhibitors complexed to the JAK1 and JAK2 protein tyrosine kinase domains Journal of molecular biology 2009 387 219 32 19361440
  34. [34]Thoma B Bird TA Friend DJ Gearing DP Dower SK Oncostatin M and leukemia inhibitory factor trigger overlapping and different signals through partially shared receptor complexes The Journal of biological chemistry 1994 269 6215 22 8119965
  35. [35]Oh H Fujio Y Kunisada K Hirota H Matsui H Kishimoto T Activation of phosphatidylinositol 3-kinase through glycoprotein 130 induces protein kinase B and p70 S6 kinase phosphorylation in cardiac myocytes The Journal of biological chemistry 1998 273 9703 10 9545305
  36. [36]Fahmi A Smart N Punn A Jabr R Marber M Heads R p42/p44-MAPK and PI3K are sufficient for IL-6 family cytokines/gp130 to signal to hypertrophy and survival in cardiomyocytes in the absence of JAK/STAT activation Cellular signalling 2013 25 898 909 23268184 PMC3627957
  37. [38]Hirai H Karian P Kikyo N Regulation of embryonic stem cell self-renewal and pluripotency by leukaemia inhibitory factor The Biochemical journal 2011 438 11 23 21793804 PMC3418323
  38. [40]Raz R Lee CK Cannizzaro LA d’Eustachio P Levy DE Essential role of STAT3 for embryonic stem cell pluripotency Proceedings of the National Academy of Sciences of the United States of America 1999 96 2846 51 10077599 PMC15857
  39. [41]Niwa H Burdon T Chambers I Smith A Self-renewal of pluripotent embryonic stem cells is mediated via activation of STAT3 Genes Dev 1998 12 2048 60 9649508 PMC316954
  40. [42]Schmitz J Dahmen H Grimm C Gendo C Muller-Newen G Heinrich PC The cytoplasmic tyrosine motifs is full-length glycoprotein 130 have different roles in IL-6 signal transduction Journal of Immunology 2000 164 848 54 10623831
  41. [43]Haan S Hemmann U Hassiepen U Schaper F Schneider-Mergener J Wollmer A Characterization and binding specificity of the monomeric STAT3-SH2 domain Journal of Biological Chemistry 1999 274 1342 8 9880505
  42. [44]Stahl N Farruggella TJ Boulton TG Zhong Z Darnell JE Jr Yancopoulos GD Choice of STATs and other substrates specified by modular tyrosine-based motifs in cytokine receptors Science 1995 267 1349 53 7871433
  43. [45]Haan S Kortylewski M Behrmann I Muller-Esterl W Heinrich PC Schaper F Cytoplasmic STAT proteins associate prior to activation Biochemical Journal 2000 345 417 21 10642496 PMC1220772
  44. [46]Starr R Willson TA Viney EM Murray LJL Rayner JR Jenkins BJ A family of cytokine-inducible inhibitors of signalling Nature 1997 387 917 21 9202125
  45. [47]Endo TA Masuhara M Yokouchi M Suzuki R Sakamoto H Mitsui K A new protein containing an SH2 domain that inhibits JAK kinases Nature 1997 387 921 4 9202126
  46. [48]Naka T Narazaki M Hirata M Matsumoto T Minamoto S Aono A Structure and function of a new STAT-induced STAT inhibitor Nature 1997 387 924 9 9202127
  47. [49]Hilton DJ Richardson RT Alexander WS Viney EM Willson TA Sprigg NS Twenty proteins containing a C-terminal SOCS box form five structural classes Proceedings of the National Academy of Sciences of the United States of America 1998 95 114 9 9419338 PMC18144
  48. [50]Babon JJ Kershaw NJ Murphy JM Varghese LN Laktyushin A Young SN Suppression of cytokine signaling by SOCS3: characterization of the mode of inhibition and the basis of its specificity Immunity 2012 36 239 50 22342841 PMC3299805
  49. [52]Kershaw NJ Laktyushin A Nicola NA Babon JJ Reconstruction of an active SOCS3-based E3 ubiquitin ligase complex in vitro: identification of the active components and JAK2 and gp130 as substrates Growth Factors 2014 32 1 10 24438103 PMC4085236
  50. [54]Roberts AW Robb L Rakar S Hartley L Cluse L Nicola NA Placental defects and embryonic lethality in mice lacking suppressor of cytokine signaling 3 Proceedings of the National Academy of Sciences of the United States of America 2001 98 9324 9 11481489 PMC55419
  51. [55]Takahashi Y Carpino N Cross JC Torres M Parganas E Ihle JN SOCS3: an essential regulator of LIF receptor signaling in trophoblast giant cell differentiation The EMBO journal 2003 22 372 84 12554639 PMC140741
  52. [56]Matsuda T Nakamura T Nakao K Arai T Katsuki M Heike T STAT3 activation is sufficient to maintain an undifferentiated state of mouse embryonic stem cells Embo Journal 1999 18 4261 9 10428964 PMC1171502
  53. [57]Paling NRD Wheadon H Bone HK Welham MJ Regulation of embryonic stem cell self-renewal by phosphoinositide 3-kinase-dependent signaling Journal of Biological Chemistry 2004 279 48063 70 15328362
  54. [58]Watanabe S Umehara H Murayama K Okabe M Kimura T Nakano T Activation of Akt signaling is sufficient to maintain pluripotency in mouse and primate embryonic stem cells Oncogene 2006 25 2697 707 16407845
  55. [60]Schiemann WP Bartoe JL Nathanson NM Box 3-independent signaling mechanisms are involved in leukemia inhibitory factor receptor alpha- and gp130-mediated stimulation of mitogen-activated protein kinase. Evidence for participation of multiple signaling pathways which converge at Ras The Journal of biological chemistry 1997 272 16631 6 9195977
  56. [61]Anhuf D Weissenbach M Schmitz J Sobota R Hermanns HM Radtke S Signal transduction of IL-6, leukemia-inhibitory factor, and oncostatin M: Structural receptor requirements for signal attenuation Journal of Immunology 2000 165 2535 43 10946280
  57. [62]Bartoe JL Nathanson NM Differential regulation of leukemia inhibitory factor-stimulated neuronal gene expression by protein phosphatases SHP-1 and SHP-2 through mitogen-activated protein kinase-dependent and -independent pathways Journal of neurochemistry 2000 74 2021 32 10800945
  58. [63]Neel BG Gu HH Pao L The ‘Shp’ing news: SH2 domain-containing tyrosine phosphatases in cell signaling Trends in Biochemical Sciences 2003 28 284 93 12826400
  59. [64]Lehmann U Schmitz J Weissenbach M Sobota RM Hortner M Friederichs K SHP2 and SOCS3 contribute to Tyr-759-dependent attenuation of interleukin-6 signaling through gp130 Journal of Biological Chemistry 2003 278 661 71 12403768
  60. [65]Burdon T Stracey C Chambers I Nichols J Smith A Suppression of SHP-2 and ERK signalling promotes self-renewal of mouse embryonic stem cells Developmental biology 1999 210 30 43 10364425
  61. [66]Meloche S Vella FD Voisin L Ang SL Saba-El-Leil M Erk2 signaling and early embryo stem cell self-renewal Cell cycle 2004 3 241 3 14726711
  62. [67]Forrai A Boyle K Hart AH Hartley L Rakar S Willson TA Absence of suppressor of cytokine signalling 3 reduces self-renewal and promotes differentiation in murine embryonic stem cells Stem cells 2006 24 604 14 16123385
  63. [69]Nichols J Chambers I Taga T Smith A Physiological rationale for responsiveness of mouse embryonic stem cells to gp130 cytokines Development 2001 128 2333 9 11493552
  64. [71]Yang J van Oosten AL Theunissen TW Guo G Silva JC Smith A Stat3 activation is limiting for reprogramming to ground state pluripotency Cell stem cell 2010 7 319 28 20804969 PMC3459098
  65. [72]Graf U Casanova EA Cinelli P The Role of the Leukemia Inhibitory Factor (LIF) - Pathway in Derivation and Maintenance of Murine Pluripotent Stem Cells Genes 2011 2 280 97 24710148 PMC3924847
  66. [73]Matsui Y Toksoz D Nishikawa S Nishikawa S Williams D Zsebo K Effect of Steel factor and leukaemia inhibitory factor on murine primordial germ cells in culture Nature 1991 353 750 2 1719421
  67. [74]Leitch HG Nichols J Humphreys P Mulas C Martello G Lee C Rebuilding pluripotency from primordial germ cells Stem cell reports 2013 1 66 78 24052943 PMC3757743
  68. [75]Stewart CL Kaspar P Brunet LJ Bhatt H Gadi I Kontgen F Blastocyst implantation depends on maternal expression of leukaemia inhibitory factor Nature 1992 359 76 9 1522892
  69. [76]Charnock-Jones DS Sharkey AM Fenwick P Smith SK Leukaemia inhibitory factor mRNA concentration peaks in human endometrium at the time of implantation and the blastocyst contains mRNA for the receptor at this time Journal of reproduction and fertility 1994 101 421 6 7932378
  70. [77]Chen JR Cheng JG Shatzer T Sewell L Hernandez L Stewart CL Leukemia inhibitory factor can substitute for nidatory estrogen and is essential to inducing a receptive uterus for implantation but is not essential for subsequent embryogenesis Endocrinology 2000 141 4365 72 11108244
  71. [78]Krishnan T Winship A Sonderegger S Menkhorst E Horne AW Brown J The role of leukemia inhibitory factor in tubal ectopic pregnancy Placenta 2013 34 1014 9 24074901
  72. [79]Laird SM Tuckerman EM Dalton CF Dunphy BC Li TC Zhang X The production of leukaemia inhibitory factor by human endometrium: presence in uterine flushings and production by cells in culture Human reproduction 1997 12 569 74 9130761
  73. [80]Giess R Tanasescu I Steck T Sendtner M Leukaemia inhibitory factor gene mutations in infertile women Molecular human reproduction 1999 5 581 6 10341007
  74. [81]White CA Zhang JG Salamonsen LA Baca M Fairlie WD Metcalf D Blocking LIF action in the uterus by using a PEGylated antagonist prevents implantation: a nonhormonal contraceptive strategy Proceedings of the National Academy of Sciences of the United States of America 2007 104 19357 62 18042698 PMC2148294
  75. [82]Lemons AR Naz RK Birth control vaccine targeting leukemia inhibitory factor Molecular reproduction and development 2012 79 97 106 22139866 PMC3261357
  76. [83]Fitzgerald JS Tsareva SA Poehlmann TG Berod L Meissner A Corvinus FM Leukemia inhibitory factor triggers activation of signal transducer and activator of transcription 3, proliferation, invasiveness, and altered protease expression in choriocarcinoma cells The international journal of biochemistry & cell biology 2005 37 2284 96 16125646
  77. [84]Horita H Kuroda E Hachisuga T Kashimura M Yamashita U Induction of prostaglandin E2 production by leukemia inhibitory factor promotes migration of first trimester extravillous trophoblast cell line, HTR-8/SVneo Human reproduction 2007 22 1801 9 17525067
  78. [85]Robb L Boyle K Rakar S Hartley L Lochland J Roberts AW Genetic reduction of embryonic leukemia-inhibitory factor production rescues placentation in SOCS3-null embryos but does not prevent inflammatory disease Proceedings of the National Academy of Sciences of the United States of America 2005 102 16333 8 16258063 PMC1283454
  79. [86]Kritikou EA Sharkey A Abell K Came PJ Anderson E Clarkson RW A dual, non-redundant, role for LIF as a regulator of development and STAT3-mediated cell death in mammary gland Development 2003 130 3459 68 12810593
  80. [87]Walker EC McGregor NE Poulton IJ Solano M Pompolo S Fernandes TJ Oncostatin M promotes bone formation independently of resorption when signaling through leukemia inhibitory factor receptor in mice The Journal of clinical investigation 2010 120 582 92 20051625 PMC2810087
  81. [88]Metcalf D Gearing DP Fatal syndrome in mice engrafted with cells producing high levels of the leukemia inhibitory factor Proceedings of the National Academy of Sciences of the United States of America 1989 86 5948 52 2569739 PMC297748
  82. [89]Metcalf D Nicola NA Gearing DP Effects of injected leukemia inhibitory factor on hematopoietic and other tissues in mice Blood 1990 76 50 6 2114187
  83. [90]Sims NA Johnson RW Leukemia inhibitory factor: a paracrine mediator of bone metabolism Growth factors 2012 30 76 87 22304408
  84. [91]Palmqvist P Persson E Conaway HH Lerner UH IL-6, leukemia inhibitory factor, and oncostatin M stimulate bone resorption and regulate the expression of receptor activator of NF-kappa B ligand, osteoprotegerin, and receptor activator of NF-kappa B in mouse calvariae Journal of immunology 2002 169 3353 62 12218157
  85. [92]Dagoneau N Scheffer D Huber C Al-Gazali LI Di Rocco M Godard A Null leukemia inhibitory factor receptor (LIFR) mutations in Stuve-Wiedemann/Schwartz-Jampel type 2 syndrome American journal of human genetics 2004 74 298 305 14740318 PMC1181927
  86. [93]Chesnokova V Auernhammer CJ Melmed S Murine leukemia inhibitory factor gene disruption attenuates the hypothalamo-pituitary-adrenal axis stress response Endocrinology 1998 139 2209 16 9564824
  87. [94]Akita S Readhead C Stefaneanu L Fine J Tampanaru-Sarmesiu A Kovacs K Pituitary-directed leukemia inhibitory factor transgene forms Rathke’s cleft cysts and impairs adult pituitary function. A model for human pituitary Rathke’s cysts The Journal of clinical investigation 1997 99 2462 9 9153290 PMC508087
  88. [95]Yano H Readhead C Nakashima M Ren SG Melmed S Pituitary-directed leukemia inhibitory factor transgene causes Cushing’s syndrome: neuro-immune-endocrine modulation of pituitary development Molecular endocrinology 1998 12 1708 20 9817597
  89. [96]Patterson PH Nawa H Neuronal differentiation factors/cytokines and synaptic plasticity Cell 1993 72 Suppl 123 37 8428374
  90. [97]Rao MS Sun Y Escary JL Perreau J Tresser S Patterson PH Leukemia inhibitory factor mediates an injury response but not a target-directed developmental transmitter switch in sympathetic neurons Neuron 1993 11 1175 85 7506046
  91. [98]Murphy M Reid K Hilton DJ Bartlett PF Generation of sensory neurons is stimulated by leukemia inhibitory factor Proceedings of the National Academy of Sciences of the United States of America 1991 88 3498 501 1901659 PMC51475
  92. [99]Murphy M Dutton R Koblar S Cheema S Bartlett P Cytokines which signal through the LIF receptor and their actions in the nervous system Progress in neurobiology 1997 52 355 78 9304697
  93. [100]Hendry IA Murphy M Hilton DJ Nicola NA Bartlett PF Binding and retrograde transport of leukemia inhibitory factor by the sensory nervous system The Journal of neuroscience: the official journal of the Society for Neuroscience 1992 12 3427 34 1527587 PMC6575741
  94. [101]Curtis R Scherer SS Somogyi R Adryan KM Ip NY Zhu Y Retrograde axonal transport of LIF is increased by peripheral nerve injury: correlation with increased LIF expression in distal nerve Neuron 1994 12 191 204 7507340
  95. [102]Richards LJ Kilpatrick TJ Dutton R Tan SS Gearing DP Bartlett PF Leukaemia inhibitory factor or related factors promote the differentiation of neuronal and astrocytic precursors within the developing murine spinal cord The European journal of neuroscience 1996 8 291 9 8714700
  96. [103]Cheema SS Richards LJ Murphy M Bartlett PF Leukaemia inhibitory factor rescues motoneurones from axotomy-induced cell death Neuroreport 1994 5 989 92 8061310
  97. [104]Kwon YW Abbondanzo SJ Stewart CL Gurney ME Leukemia inhibitory factor influences the timing of programmed synapses withdrawal from neonatal muscles Journal of neurobiology 1995 28 35 50 8586964
  98. [105]Sendtner M Gotz R Holtmann B Escary JL Masu Y Carroll P Cryptic physiological trophic support of motoneurons by LIF revealed by double gene targeting of CNTF and LIF Current biology: CB 1996 6 686 94 8793295
  99. [106]Li M Sendtner M Smith A Essential function of LIF receptor in motor neurons Nature 1995 378 724 7 7501019
  100. [107]DeChiara TM Vejsada R Poueymirou WT Acheson A Suri C Conover JC Mice lacking the CNTF receptor, unlike mice lacking CNTF, exhibit profound motor neuron deficits at birth Cell 1995 83 313 22 7585948
  101. [108]Bauer S Patterson PH Leukemia inhibitory factor promotes neural stem cell self-renewal in the adult brain The Journal of neuroscience: the official journal of the Society for Neuroscience 2006 26 12089 99 17108182 PMC6674883
  102. [109]Yoshida T Satoh M Nakagaito Y Kuno H Takeuchi M Cytokines affecting survival and differentiation of an astrocyte progenitor cell line Brain research Developmental brain research 1993 76 147 50 8306427
  103. [110]Ware CB Horowitz MC Renshaw BR Hunt JS Liggitt D Koblar SA Targeted disruption of the low-affinity leukemia inhibitory factor receptor gene causes placental, skeletal, neural and metabolic defects and results in perinatal death Development 1995 121 1283 99 7789261
  104. [111]Mayer M Bhakoo K Noble M Ciliary neurotrophic factor and leukemia inhibitory factor promote the generation, maturation and survival of oligodendrocytes in vitro Development 1994 120 143 53 8119123
  105. [112]Deverman BE Patterson PH Exogenous leukemia inhibitory factor stimulates oligodendrocyte progenitor cell proliferation and enhances hippocampal remyelination The Journal of neuroscience: the official journal of the Society for Neuroscience 2012 32 2100 9 22323722 PMC3561904
  106. [113]Bugga L Gadient RA Kwan K Stewart CL Patterson PH Analysis of neuronal and glial phenotypes in brains of mice deficient in leukemia inhibitory factor Journal of neurobiology 1998 36 509 24 9740023
  107. [114]Ishibashi T Lee PR Baba H Fields RD Leukemia inhibitory factor regulates the timing of oligodendrocyte development and myelination in the postnatal optic nerve Journal of neuroscience research 2009 87 3343 55 19598242 PMC2782399
  108. [115]Austin L Burgess AW Stimulation of myoblast proliferation in culture by leukaemia inhibitory factor and other cytokines Journal of the neurological sciences 1991 101 193 7 1903437
  109. [116]Barnard W Bower J Brown MA Murphy M Austin L Leukemia inhibitory factor (LIF) infusion stimulates skeletal muscle regeneration after injury: injured muscle expresses lif mRNA Journal of the neurological sciences 1994 123 108 13 8064301
  110. [117]Finkelstein DI Bartlett PF Horne MK Cheema SS Leukemia inhibitory factor is a myotrophic and neurotrophic agent that enhances the reinnervation of muscle in the rat Journal of neuroscience research 1996 46 122 8 8892113
  111. [118]Sakuma K Watanabe K Sano M Uramoto I Totsuka T Differential adaptation of growth and differentiation factor 8/myostatin, fibroblast growth factor 6 and leukemia inhibitory factor in overloaded, regenerating and denervated rat muscles Biochimica et biophysica acta 2000 1497 77 88 10838161
  112. [119]Spangenburg EE Booth FW Leukemia inhibitory factor restores the hypertrophic response to increased loading in the LIF(−/−) mouse Cytokine 2006 34 125 30 16781162
  113. [120]Kurek JB Bower JJ Romanella M Koentgen F Murphy M Austin L The role of leukemia inhibitory factor in skeletal muscle regeneration Muscle & nerve 1997 20 815 22 9179153
  114. [121]Sheng Z Pennica D Wood WI Chien KR Cardiotrophin-1 displays early expression in the murine heart tube and promotes cardiac myocyte survival Development 1996 122 419 28 8625793
  115. [122]Nelson SK Wong GH McCord JM Leukemia inhibitory factor and tumor necrosis factor induce manganese superoxide dismutase and protect rabbit hearts from reperfusion injury Journal of molecular and cellular cardiology 1995 27 223 9 7760346
  116. [123]Zou Y Takano H Mizukami M Akazawa H Qin Y Toko H Leukemia inhibitory factor enhances survival of cardiomyocytes and induces regeneration of myocardium after myocardial infarction Circulation 2003 108 748 53 12860906
  117. [124]Mohri T Fujio Y Maeda M Ito T Iwakura T Oshima Y Leukemia inhibitory factor induces endothelial differentiation in cardiac stem cells The Journal of biological chemistry 2006 281 6442 7 16407199
  118. [125]Leary AG Wong GG Clark SC Smith AG Ogawa M Leukemia inhibitory factor differentiation-inhibiting activity/human interleukin for DA cells augments proliferation of human hematopoietic stem cells Blood 1990 75 1960 4 1692490
  119. [126]Metcalf D The unsolved enigmas of leukemia inhibitory factor Stem cells 2003 21 5 14 12529546
  120. [127]Escary JL Perreau J Dumenil D Ezine S Brulet P Leukaemia inhibitory factor is necessary for maintenance of haematopoietic stem cells and thymocyte stimulation Nature 1993 363 361 4 8497320
  121. [128]Metcalfe SM LIF in the regulation of T-cell fate and as a potential therapeutic Genes and immunity 2011 12 157 68 21368774
  122. [129]Weber MA Schnyder-Candrian S Schnyder B Quesniaux V Poli V Stewart CL Endogenous leukemia inhibitory factor attenuates endotoxin response Laboratory investigation; a journal of technical methods and pathology 2005 85 276 84 15702085
  123. [130]Liu SC Tsang NM Chiang WC Chang KP Hsueh C Liang Y Leukemia inhibitory factor promotes nasopharyngeal carcinoma progression and radioresistance The Journal of clinical investigation 2013 123 5269 83 24270418 PMC3859424
  124. [131]Wu L Yu H Zhao Y Zhang C Wang J Yue X HIF-2alpha mediates hypoxia-induced LIF expression in human colorectal cancer cells Oncotarget 2015 6 4406 17 25726527 PMC4414199
  125. [132]Yu H Yue X Zhao Y Li X Wu L Zhang C LIF negatively regulates tumour-suppressor p53 through Stat3/ID1/MDM2 in colorectal cancers Nature communications 2014 5 5218 PMC4203416 25323535
  126. [133]Davis ID Kiers L MacGregor L Quinn M Arezzo J Green M A randomized, double-blinded, placebo-controlled phase II trial of recombinant human leukemia inhibitory factor (rhuLIF, emfilermin, AM424) to prevent chemotherapy-induced peripheral neuropathy Clinical cancer research: an official journal of the American Association for Cancer Research 2005 11 1890 8 15756015
  127. [134]Gunawardana DH Basser RL Davis ID Cebon J Mitchell P Underhill C A phase I study of recombinant human leukemia inhibitory factor in patients with advanced cancer Clinical cancer research: an official journal of the American Association for Cancer Research 2003 9 2056 65 12796368
  128. [135]Brinsden PR Alam V de Moustier B Engrand P Recombinant human leukemia inhibitory factor does not improve implantation and pregnancy outcomes after assisted reproductive techniques in women with recurrent unexplained implantation failure Fertility and sterility 2009 91 1445 7 18710712

Cited by

Sorted by citations

Authors
Nicola, N. A., & Babon, J. J.
Affiliations
The University of Melbourne (AU)
Corresponding author
Nicola, Nicos A.
ORCID
Venue
Cytokine & Growth Factor Reviews
Publisher
Elsevier BV
Published
2015-10
Volume
26
Issue
5
Pages
533-544
ISSN
1359-6101 (ISSN-L)
DOI
10.1016/j.cytogfr.2015.07.001
PMC
PMC4581962
OpenAlex
W1824670638
Cited by
478
References
7
Citations by year
2026: 42 · 2025: 48 · 2024: 60 · 2023: 53 · 2022: 64 · 2021: 51 · 2020: 50 · 2019: 39 · 2018: 25 · 2017: 20 · 2016: 20 · 2015: 3 · 2014: 1
FWCI
2.44
Type
journal article
Language
en
Open access
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Cytokine & Growth Factor Reviews (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Health and Medical Research Council (461219, 1016647, 637300, 1078737)
  • The Independent Research Institutes Infrastructure
  • Australian Research Council (FT110100169)
  • National Institutes of Health (RO1CA22556)
  • State Government of Victoria
Topics
  • Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Growth Hormone and Insulin-like Growth Factors
Keywords
leukemia inhibitory factor, interleukin-6 family cytokines, gp130, ciliary neurotrophic factor, oncostatin M, cardiotrophin-1, JAK/STAT signaling, MAPK signaling, PI3K signaling, cell proliferation, cell differentiation, cell survival, embryo implantation, placental development, brain development, embryonic stem cell self-renewal, induced pluripotent stem cells, totipotency
MeSH terms
Human Embryonic Stem Cells, Mouse Embryonic Stem Cells, Animals, Blastocyst, Gene Expression Regulation, Humans, Embryo Implantation, Mice, Knockout, Phosphatidylinositol 3-Kinases, MAP Kinase Signaling System, STAT Transcription Factors, Cytokine Receptor gp130, Mice, Leukemia Inhibitory Factor, Receptors, OSM-LIF, Janus Kinases

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