Leukaemia inhibitory factor

Matsui, Y Toksoz, D., Nishikawa, S., Nishikawa, S-I., Williams, D Zsebo, K., and Hogan, B. L. M. (1991). Effect of Steel factor and leukaemia inhibitory factor on murine primordial germ cells in culture. Nature 353 750-752. 

Interleukin 1 (IL-1) is produced mainly by activated monocytes-macropha-ges, and its principal action is to stimulate thymocytes. A pleiotropic cytokine, IL-1 induces the expression of a large diversity of cytokines such as IL-6, leukaemia inhibitory factor (LIF), and other proinflammatory molecules (Di-marello 1994). IL-1 and TNF-a carry out as part of their function increasing the expression of NF-/cB and JNK (c-Jun N-terminal kinase). The importance of IL-1 in OCS is demonstrated because the IL-1-receptor-deficient mouse is resistant to ovariectomy (OVX)-induced bone loss (Lorenzo et al. 1998). The importance in pathological bone loss is also illustrated by the fact that treatment with IL-1 receptor antagonist slows down bone erosion for patients affected with rheumatoid arthritis (Kwan et al. 2004). IL-1 increases osteoclast differentiation rather than mature osteoclast activity, and infusion of IL-1 into mice induces hypercalcemia and bone resorption. Finally, IL-1 and TNF-a... 

Leukaemia inhibitory factor (LIF) Autocrine/paracrine Preadipocytes Promotes adipogenesis... 

Williams RL, Hilton DJ, Pease S, Wilson TA, Stewart CL, Gearing DP, Wagner EF, Metcalf D, Nicola NA, Gough NM. Myeloid leukaemia inhibitory factor maintains the developmental potential of embryonic stem cells. Nature 1988 336 684-687. 

Haematopoietins Interleukins 2-7, -9, -13 Granulocyte colony stimulating factor Granulocyte-macrophage colony stimulating factor Leukaemia inhibitory factor Erythropoietin Ciliary neurotrophic factor... 

Figure 4.1. Cytokine receptors usually display a unique cytokine ( ligand )-binding domain, but share additional receptor components, which are normally responsible for signal transduction. This explains the molecular basis of pleiotropy. IL-6, IL-11 and leukaemia inhibitory factor (LIF), for example, are all composed of a distinct ligand-specific binding domain, and a separate subunit (gpl30). gpl30 is responsible for initiating signal transduction and is identical in all three receptors. This is depicted schematically above...

Leukaemia inhibitory factor Mainly various haemopoietic cells... 

When the embryo arrives in the uterine cavity, the trophectoderm infiltrates the uterine epithelium by a poorly characterized mechanism. Several maternal and embryonic factors are crucial to implantation. These factors include colony stimulating factor, leukaemia inhibitory factor, interleukin- and several proteolytic enzymes. Before the placenta develops, the implanted embryo is nourished by histotrophic material from degradation of endometrial cells during implantation. The embryo is also nourished by secretions from endometrial glands and by the yolk sac the latter persists for different time periods and plays different roles in different species. 

Harvey, M B., Leco, K. J., Arcellana-Panlilio, M Y, Zhang, X., Edwards, D. R., and Schultz, G. A. (1995) Proteinase expression m early mouse embryos is regulated by leukaemia inhibitory factor and epidermal growth factor. Development 121, 1005-1014. 

Leukaemia inhibitory factor LIFRa (gpl90) LIF RMT Blood to brain/spinal cord [48]... 

Pan, W., A.J. Kastin, and J.M. Brennan. 2000. Saturable entry of leukaemia inhibitory factor from blood to the central nervous system. J Neuroimmunol 106 172. 

Cytokine subfamily 2 includes proteins with heterodimeric a—(3 or ct-gpl30 receptors. Thus, granulocyte macrophage colony stimulating factor (GM-GSF), IL-3 and IL-5 act via a—(3 receptors and share (3 receptors. Cardiotrophin-1 (GT-1), ciliary neurotrophic factor (CTNF), IL-6, IL-1, leukaemia inhibitory factor (LIF) and oncostatin M (OSM) act via heterodimeric a-gpl30 receptors with a shared gpl30 receptor subunit. Leucocyte-derived cytokines of this family have immunomodulatory and haematopoietic effects. 

Aasland, D., Oppmann, B., Grotzinger, J., Rose-John, S., and Kallen, K. J. (2002). The upper cytokine-binding module and the Ig-like domain of the leukaemia inhibitory factor (LIF) receptor are sufficient for a functional LIF receptor complex. J. Mol. Biol. 315, 637-646. 

Austin, L., Burgess, A.W. (1991). Stimulation of myoblast proliferation in culture by leukaemia inhibitory factor and other cytokines. J. Neurol Sci. 101 193-7. 

Austin, L., Bower, J., Kurek, J., Vakakis N. (1992). Effects of leukaemia inhibitory factor and other cytokines on murine and human myoblast proliferation. J. Neurol. Sci. 112 185-91. 

Coyle P, Philcox JC, Rofe AM. Metallothionein induction in cultured rat hepatocytes by arthritic rat serum, activated macrophages, interleukin-6, interleukin-11 and leukaemia inhibitory factor. Inflamm Res 1996 44 475-81. 

Gabay C, Singwe M, Genin B, et al. Circulating levels of IL-11 and leukaemia inhibitory factor (LIF) do not significantly participate in the production of acute-phase proteins by the liver. Clin Exp Immunol 1996 105 260-5. 

Kurek JB, Austin L, Cheema SS, et al. Up-regulation of leukaemia inhibitory factor and interleukin-6 in transected sciatic nerve and muscle following denervation. Neuromuscul Disord 1996 6 105-14. 

N.A., Simpson, R.J., Nice, E.C., Kelso, A. and Metcalf, D. (1987) Molecular cloning and expression of cDNA encoding a murine myeloid leukaemia inhibitory factor (LIF). EMBO J. 6 3995 002. 

Anegon, I., Cuturi, M.C., Godard, A., Moreau, M., Terqui, M., Martinat- Botte, F. and Soulillou, J.P. (1994) Presence of leukaemia inhibitory factor and interleukin 6 in porcine uterine seeretions prior to conceptus attachment. Cytokine 6 493 99. 

Charnock-Jones, D.S., Sharkey, A.M., Fenwick, P. and Smith, S.K. (1994) 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. J. Reprod. Fertil. 101 421-426. 

Cheema, S.S., Richards, L.J., Murphy, M. and Bartlett, P.F. (1994b) Leukaemia inhibitory factor rescues motoneurones from axotomy-induced cell death. NeuroReport 5 989-992. 

Escary, J.-L., Perreau, J., Dumenil, D., Ezine, S. and Brfllet, P. (1993) Leukaemia inhibitory factor is necessary for maintenance of haematopoietic stem cells and thymocyte stimulation. Nature 363 361-364. 

Smith, D.K., Treutlein, H.R., Maurer, T., Owczarek, C.M., Layton, M.J., Nicola, N.A. and Norton, R.S. (1994) Homology modelling and IHNMR studies of human leukaemia inhibitory factor. FEBS Lett. 350 275-280. 

Stewart, C.L., Kaspar, P., Brunet, L.J., Bhatt, H., Gadi, 1., Kdntgen, F. and Abbondanzo, S.J. (1992) Blastocyst implantation depends on maternal expression of leukaemia inhibitory factor. Nature 359 76-79. 

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