Interleukin-6 family of cytokines and gp130

Blood

Volumn 86, Issue 4, 1995, Pages 1243-1254

  Kishimoto, Tadamitsu ^a   Akira, Shizuo ^b   Narazaki, Masashi ^b   Taga, Tetsuya ^b  

^a OSAKA UNIVERSITY MEDICAL SCHOOL   (Japan)

^b NONE

Author keywords

[No Author keywords available]

Indexed keywords

INTERLEUKIN 6; INTERLEUKIN RECEPTOR;

CELL DIFFERENTIATION; GROWTH REGULATION; HEMATOPOIESIS; HEMATOPOIETIC CELL; HEMATOPOIETIC STEM CELL; HUMAN; PRIORITY JOURNAL; REVIEW;

EID: 0029084805     PISSN: 00064971     EISSN: None     Source Type: Journal    
DOI: 10.1182/blood.v86.4.1243.bloodjournal8641243     Document Type: Review

References (116)

1. Hirano T, Taga T, Nakano N, Yasukawa K, Kashiwamura S, Shimizu K, Nakajima K, Pyun KH, Kishimoto T: Purification to homogeneity and characterization of human B-cell differentiation factor(BCDF or BSFp-2). Proc Natl Acad Sci USA 85:5490, 1985
2. Hirano T, Yasukawa K, Harada H, Taga T, Watanabe Y, Matsuda T, Kashiwamura S-I, Nakajima K, Koyama K, Iwamatsu A, Tsunasawa S, Sakiyama F, Matsui H, Takahara Y, Taniguchi T, Kishimoto T: Complementary DNA for a novel human interleukin (BSF-2) that induces B lymphocytes to produce immunoglobulin. Nature 324:73, 1986
3. Kishimoto T: The biology of interleukin-6. Blood 74:1, 1989
4. Kishimoto T, Akira S, Taga T: Interleukin-6 and its receptor: A paradigm for cytokines. Science 258:593, 1992
5. Akira S, Taga T, Kishimoto T: Interleukin-6 in biology and medicine. Adv Immunol 54:1, 1993
6. Van Damme J, Opdenakker G, Simpson R, Rubira MR, Cayphas S, Vink A, Billiau A, Van Snick J: Identification of the human 26-kD protein, interferon β2, as a cell hybridoma/plasmacytoma growth factor induced by interleukin-1 and tumor necrosis factor. J Exp Med 165:914, 1987
7. Kawano M, Hirano T, Matsuda T, Taga T, Horii Y, Iwato K, Asaoku H, Tang B, Tanabe O, Tanaka H, Kuramoto A, Kishimoto T: Autocrine generation and essential requirement of BSF-2/IL-6 for human multiple myelomas. Nature 332:83, 1988
8. Suematsu S, Matsusaka T, Matsuda T, Ohno S, Miyazaki J, Yamamura K, Hirano T, Kishimoto T: Generation of plasmacytomas with the chromosomal translocations t(12;5) in IL-6 transgenic mice. Proc Natl Acad Sci USA 89:232, 1992
9. Schwab G, Siegall CB, Aarden LA, Neckers LM, Nordan RP: Characterization of an interleukin-6-mediated autocrine growth loop in the human multiple myeloma cell line, U266. Blood 77:587, 1991
10. Klein B, Zhang XG, Jourdan M, Content J, Houssiau F, Aarden L, Piechaczyk M, Bataille R: Paracrine rather than autocrine regulation of myeloma-cell growth and differentiation by interleukin-6. Blood 73:517, 1989
11. Klein B, Wijdenes J, Zhang XG, Jourdan M, Boiron JM, Brochier J, Liautard J, Merlin M, Clement C, Mortel-Fourniel B: Murine anti-interleukin-6 monoclonal antibody therapy for a patient with plasma cell leukemia. Blood 78:1198, 1991
12. Shabo Y, Lotem J, Rubinstein M, Revel M, Clark SC, Wolf SF, Kamen R, Sachs L: The myeloid blood cell differentiationinducing protein MGI-2A is interleukin 6. Blood 72:2070, 1988
13. Miyaura C, Onozaki K, Akiyama Y, Taniyama T, Hirano T, Kishimoto T, Suda T: Recombinant human interleukin 6 (B-cell stimulatory factor 2) is a potent inducer of differentiation of mouse myeloid leukemia cells (M1). FEBS Lett 234:17, 1988
14. Hilton DJ, Gough NM: Leukemia inhibitory factor: A biological perspective. J Cell Biochem 46:21, 1991
15. Gearing DP, Comeau MR, Friend DJ, Gimpel SD, Thut CJ, McGourty J, Brasher KK, King JA, Gillis S, Mosley B, Ziegler SF, Cosman D: The IL-6 signal transducer, gp130: An oncostatin M receptor and affinity converter for the LIF receptor. Science 255:1434, 1992
16. Ip NY, Nye SH, Boulton TG, Davis S, Taga T, Li Y, Birren SJ, Yasukawa K, Kishimoto T, Anderson DJ, Stahl N, Yancopoulos GD: CNTF and LIF act on neuronal cells via shared signaling pathways that involve the IL-6 signal transducing receptor component gp130. Cell 69:1121, 1992
17. Taga T, Narazaki M, Yasukawa K, Saito T, Miki D, Hamaguchi M, Davis S, Shoyab M, Yancopoulos GD, Kishimoto T: Functional inhibition of hematopoietic- and neurotrophic-cytokines by blocking the IL-6 signal transducer, gp130. Proc Natl Acad Sci USA 89:10998, 1992
18. Ikebuchi K, Wong GG, Clark SC, Ihle JN, Hirai Y, Ogawa M: Interleukin-6 enhancement of interleukin-3-dependent proliferation of multipotential hemopoietic progenitors. Proc Natl Acad Sci USA 84:9035, 1987
19. Suzuki C, Okano A, Takatsuki F, Miyasaka Y, Hirano T, Kishimoto T, Ejima D, Akiyama Y: Continuous perfusion with interleukin 6 (IL-6) enhances production of hematopoietic stem cells (CFU-s). Biochem Biophys Res Commun 159:933, 1989
20. Okano A, Suzuki C, Takatsuki F, Akiyama Y, Koike K, Nakahata T, Hirano T, Kishimoto T, Ozawa K, Asano S: In vitro expansion of murine pluripotent hemopoietic stem cell population in response to interleukin 3 and interleukin 6: Application to bone marrow transplantation. Transplantation 48:495, 1989
21. Andus T, Geiger T, Hirano T, Northoff H, Ganter U, Bauer J, Kishimoto T, Heinrich PC: Recombinant human B cell stimulatory factor 2 (BSF-2/IFN-β2) regulates β-fibrinogen and albumin mRNA levels in Fao-9 cells. FEBS Lett 221:18, 1987
22. 2/B cell stimulating factor type 2 shares identity with monocyte-derived hepatocyte stimulating factor and regulates the major acute phase protein response in liver cells. Proc Natl Acad Sci USA 84:7251, 1987
23. Baumann H, Wong GG: Hepatocyte-stimulating factor III shares structural and functional indentity with leukemia-inhibitory factor. J Immunol 143:1163, 1989
24. Baumann H, Schendel P: Interleukin-11 regulates the hepatic expression of the same plasma protein genes as interleukin-6. J Biol Chem 266:20424, 1992
25. Richard CD, Brown TJ, Shoyab M, Baumann H, Gauldie J: Recombinant oncostatin M stimulates the production of acute phase proteins in HepG2 cells and rat primary hepatocytes in vitro. J Immunol 148:1731, 1992
26. Kopf M, Lamers M, Bluethman H, Köhler G: IL-6 deficient mice show immunologic abnormalities. Nature 376:339, 1994
27. Yamasaki K, Taga T, Hirata Y, Yawata H, Kawanishi Y, Seed B, Taniguchi T, Hirano T, Kishimoto T: Cloning and expression of the human interleukin-6 (BSF-2/IFN b 2) receptor. Science 241:825, 1988
28. Yawata H, Yasukawa K, Natsuka S, Murakami M, Yamasaki K, Hibi M, Taga T, Kishimoto T: Structure-function analysis of human IL-6 receptor: Dissociaton of amino acid residues required for IL-6-binding and for IL-6 signal transduction through gp130. EMBO J 12:1705, 1993
29. Bazan JF: Structural design and molecular evolution of a cytokine receptor superfamily. Proc Natl Acad Sci USA 87:6934, 1990
30. Bazan JF: Haemopoietic receptors and helical cytokines. Immunol Today 11:350, 1990
31. Taga T, Kishimoto T: Cytokine receptors and signal transduction. FASEB J 6:3387, 1992
32. Miyajima A, Kitamura T, Harada N, Yokota T, Arai K: Cytokine receptors and signal transduction. Annu Rev Immunol 10:295, 1992
33. Patthy L: Homology of a domain of the growth hormone/ prolactin receptor family with type III modules of fibronectin. Cell 61:13, 1990
34. De Vos AM, Ultsch M, Kossiakoff AA: Human growth hormone and extracellular domain of its receptor: Crystal structure of the complex. Science 225:306, 1992
35. Taga T, Hibi M, Hirata Y, Yamasaki K, Yasukawa K, Matsuda T, Hirano T, Kishimoto T: Interleukin-6 triggers the association of its receptor with a possible signal transducer, gp130. Cell 58:573, 1989
36. Hibi M, Murakami M, Saito M, Hirano T, Taga T, Kishimoto T: Molecular cloning and expression of an IL-6 signal transducer, gp130. Cell 63:1149, 1990
37. Saito M, Yoshida K, Hibi M, Taga T, Kishimoto T: Molecular cloning of a murine IL-6 receptor-associated signal transducer, gp130, and its regulated expression in vivo. J Immunol 148:4066, 1992
38. Pennica D, King K, Shaw KJ, Luis E, Rullamas J, Luoh S-M, Darbonne WC, Knutzon DS, Yen R, Chien KR, Baker JB, Wood W: Expression cloning of cardiotrophin 1, a cytokine that induces cardiac myocyte hypertrophy. Proc Natl Acad Sci USA 92:1142, 1995
39. Pennica D, Shaw KJ, Swanson TA, Moore MW, Shelton DL, Zioncheck KA, Rosenthal A, Taga T, Paoni NF, Wood WI; Cardiotrophin-1: Biological activities and binding to the leukemia inhibitory factor receptor/gp130 signaling complex. J Biol Chem 270:10915, 1995
40. Rose TM, Bruce AG: Oncostatin M is a member of a cytokine family that includes leukemia inhibitory factor, granulocyte colony-stimulating factor, and interleukin 6. Proc Natl Acad Sci USA 88:8641, 1991
41. Stökli KA, Lottspeich F, Sendtner M, Masaiakowski P, Carrol P, Götz R, Lindholm D, Thoenen H: Molecular cloning, expression and regional distribution of rat ciliary neurotrophic factor. Nature 342:920, 1989
42. Davis S, Aldrich TH, Valenzuela DM, Wong V, Furth ME, Squinto SP, Yancopoulos GD: The receptor for ciliary neurotrophic factor. Science 253:59, 1991
43. Davis S, Aldrich TH, Stahl N, Pan L, Taga T, Kishimoto T, Ip NY, Yancopoulos GD: LIFRβ and gp130 as heterodimerizing signal transducers of the tripartite CNTF receptor. Science 260:1805, 1993
44. Paul SR, Bennett F, Calvetti JA, Kelleher K, Wood CR, O'Hara RM, Leary AC Jr, Sibley B, Clark SC, Williams DA, Yang Y-C: Molecular cloning of a cDNA encoding interleukin-11, a stromal cell-derived lymphopoietic and hematopoietic cytokine. Proc Natl Acad Sci USA 87:7512, 1990
45. Buruno E, Briddell RA, Cooper RJ, Hoffman R: Effects of recombinant interleukin-11 on human megakaryocyte progenitor cells. Exp Hematol 19:378, 1991
46. Yin T, Taga T, Tsang ML-S, Yasukawa T, Kishimoto T, Yang YC: Involvement of interleukin-6 signal transducer gp130 in interleukin-11 mediated signal transduction. J Immunol 151:2555, 1993
47. Hilton DJ, Hilton AA, Raicevic A, Rakar S, Harrison-Smith M, Gough NM, Begley CG, Metcalf D, Nicola NA, Willson TA: Cloning of a murine IL-11 receptor α-chain: Requirement for gp130 for high affinity binding and signal transduction. EMBO J 13:4765, 1994
48. Kishimoto T, Taga T, Akira S: Cytokine signal transduction. Cell 76:253, 1994
49. Murakami M, Hibi M, Nakagawa N, Nakagawa T, Yasukawa K, Yamanishi K, Taga T, Kishimoto T: IL-6-induced homodimerization of gp130 and associated activation of a tyrosine kinase. Science 260:1808, 1993
50. Gearing DP, Thut CJ, Vandenbos T, Gimpel SD, Delaney PB, King J, Price V, Cosman D, Beckmann MP: Leukemia inhibitory factor receptor is structurally related to the IL-6 signal transducer, gp130. EMBO J 10:2839, 1991
51. Liu J, Modrell B, Aruffo A, Marken JS, Taga T, Yasukawa K, Murakami M, Kishimoto T, Shoyab M: Interleukin-6 signal transducer gp130 mediates oncostatin M signaling. J Biol Chem 267:16763, 1992
52. 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. J Biol Chem 269:6215, 1994
53. Chua AO, Chizzonite R, Desai BB, Truitt TP, Nunes P, Minetti LJ, Warrier RR, Presky DH, Levine JF, Gately MK, Gubler U: Expression cloning of a human IL-12 receptor component: A new member of the cytokine receptor superfamily with strong homology to gp130. J Immunol 153:128, 1994
54. Fukunaga R, Seto Y, Mizushima S, Nagata S: Three different mRNAs encoding human granulocyte colony-stimulating factor receptor. Proc Natl Acad Sci USA 87:8702, 1990
55. Kobayashi M, Fitz M, Ryan M, Hewick RM, Clark SC, Chan S, Loudon R, Sherman F, Perussia B, Trinchieri G: Identification and purification of natural killer cell stimulatory factor (NKSF), a cytokine with multiple biologic effects on human lymphocytes. J Exp Med 170:827, 1989
56. Gubler U, Chua AO, Schoenhaut DS, Dwyer CM, McComas W, Motyka R, Nabavi N, Wolitzky AG, Quinn PM, Familletti PF, Gately MK: Coexpression of two distinct genes is required to generate secreted bioactive cytoxic lymphocyte maturation factor. Proc Natl Acad Sci USA 88:4143, 1991
57. Wolf SF, Temple PA, Kobayashi M, Young D, Dicig M, Lowe L, Dzialo R, Fitz L, Ferenz C, Azzoni L, Chan SH, Trinchieri G, Perussia B: Cloning of cDNA for natural killer cell stimulatory factor, a heterodimeric cytokine with multiple biologic effects on T and natural killer cells. J Immunol 146:3074, 1991
58. Merberg DM, Wolf SF, Clark SC: Sequence similarity between NKSF and the IL-6/G-CSF family. Immunol Today 13:77, 1992
59. Gearing DP, Cosman D: Homology of the p40 subunit of natural killer cell stimulatory factor (NKSF) with the extracellular domain of the interleukin-6 receptor. Cell 66:9, 1991
60. Taniguchi T, Minami Y: The IL-2/1L-2 receptor system: A current overview. Cell 73:5, 1993
61. Nakamura Y, Russell SM, Mess SA, Friedmann M, Erdos M, Francois C, Jacques Y, Adelstein S, Leonard WJ: Heterodimerization of the IL-2 receptor β- and γ-chain cytoplasmic domains is required for signalling. Nature 369:330, 1994
62. Nelson BH, Lord JD, Greenberg PD: Cytoplasmic domains of the interleukin-2 receptor β and γ chains mediate the signal for T-cell proliferation. Nature 369:333, 1994
63. Russell SM, Keegan AD, Harada N, Nakamura Y, Noguchi M, Leland P, Friedmann MC, Miyajima A, Puri RK, Paul WE, Leonard WJ: Interleukin-2 receptor γ chain: A functional component of the interleukin-4 receptor. Science 262:1880, 1993
64. Noguchi M, Nakamura Y, Russell, SM, Ziegler SF, Tsang M, Cao X, Leonard WJ: Interleukin-2 receptor γ chain: A functional component of the interleukin-7 receptor. Science 262:1877, 1993
65. Kondo M, Takeshita T, Higuchi M, Nakamura M, Sudo T, Nishikawa S, Sugamura K: Functional participation of the IL-2 receptor γ chain in IL-7 receptor complexes. Science 263:1453, 1994
66. Giri JG, Ahdieh M, Eisenman J, Shanebeck K, Grabstein K, Kumaki S, Namen A, Park LS, Cosman D, Anderson D: Utilization of the β and γ chains of the IL-2 receptor by the novel cytokine IL-15. EMBO J 13:2822, 1994
67. Noguchi M, Yi H, Rosenblatt HM, Filipovich AH, Adelstein S, Modi WS, McBride OW, Leonard WJ: Interleukin-2 receptor γ chain mutation results in X-linked severe combined immunodeficiency in humans. Cell 73:147, 1993
68. Bamford RN, Grant AJ, Burton JD, Peters C, Kurys G, Goldman CK, Brennan J, Roessler E, Waldmann TA: The Interleukin (IL) 2 receptor β chain is shared by IL-2 and a cytokine, provisionally designated IL-T, that stimulates T-cell proliferation and the induction of lymphokine-activated killer cells. Proc Natl Acad Sci USA 91:4940, 1994
69. Grabstein KH, Eisenman J, Shanebeck K, Rauch C, Srinivasan S, Fung V, Beers C, Richardson J, Schoenborn MA, Ahdieh M, Johnson L, Alderson MR, Watson JD, Anderson DM, Giri JG: Cloning of a T cell growth factor that interacts with the β chain of the interleukin-2 receptor. Science 264:965, 1994
70. Taga T, Kishimoto T: Signaling mechanisms through cytokine receptors that share signal transducing receptor components. Curr Opin Immunol 7:17, 1995
71. Heldin C-H: Dimerization of cell surface receptors in signal transduction. Cell 180:213, 1995
72. Yoshida K, Chambers I, Nichols J, Smith A, Saito M, Yasukawa K, Shoyab M, Taga T, Kishimoto T: Maintenance of the pluripotential phenotype of embryonic stem cells through direct activation of gp130 signalling pathways. Mech Dev 45:163, 1994
73. Hirota H, Yoshida K, Kishimoto T, Taga T: Continuous activation of gp130, a signal transducing receptor component for IL-6-related cytokines, causes myocardial hypertrophy in mice. Proc Natl Acad Sci USA 92:4862, 1995
74. Sakamaki K, Miyajima I, Kitamura T, Miyajima A: Critical cytoplasmic domains of the common β subunit of the human GM-CSF, IL-3 and IL-5 receptors for growth signal transduction and tyrosine phosphorylation. EMBO J 11:3541, 1992
75. Takaki S, Murata Y, Kitamura T, Miyajima A, Tominaga A, Takatsu K: Reconstitution of the functional receptors for murine and human interleukin 5. J Exp Med 177:1523, 1993
76. Polotskaya A, Zhao Y, Lilly MB, Kraft AS: Mapping the intracytoplasmic regions of the a granulocyte-macrophage colony-stimulating factor receptor necessary for cell growth regulation. J Biol Chem 269:14607, 1994
77. Weiss M, Yokoyama C, Shikama Y, Naugle C, Druker B, Sieff CA: Human granulocyte-macrophage colony-stimulating factor receptor signal transduciton requires the proximal cytoplasmic domains of the α and β subunits. Blood 82:3298, 1993
78. Murakami M, Narazaki M, Hibi M, Yawata H, Yasukawa K, Hamaguchi M, Taga T, Kishimoto T: Critical cytoplasmic region of the IL-6 signal transducer, gp130, is conserved in the cytokine receptor family. Proc Natl Acad Sci USA 88:11349, 1991
79. yes tyrosine kinase. J Immunol 149:1676, 1992
80. Ernst M, Gearing DP, Dunn AR: Functional and biochemical association of Hck with the LIF/IL-6 receptor signal transducing subunit gp130 in embryonic stem cells. EMBO J 13:1574, 1994
81. Witthuhn BA, Quelle FW, Silvennoinen O, Yi T, Tang B, Miura O, Ihle JN: JAK2 associates with the erythropoietin receptor and is tyrosine phosphorylated and activated following stimulation with erythropoietin. Cell 74:227, 1993
82. Silvennoinen O, Witthuhn BA, Quelle FW, Cleveland JL, Yi T, Ihle JN: Structure of the JAK2 protein tyrosine kinase and its role in IL-3 signal transduction. Proc Natl Acad Sci USA 90:1429, 1993
83. Argetsinger LS, Campbell GS, Yang X, Witthuhn BA, Silvennoinen O, Ihle JN, Carter-Su C: Identification of JAk2 as a growth hormone receptor-associated tyrosine kinase. Cell 74:237, 1993
84. Lütticken C, Wegenka UM, Yuan J, Buschmann J, Schindler C, Ziemiecki A, Harpur AG, Wilks AF, Yasukawa K, Taga T, Kishimoto T, Barbieri G, Pellegrini S, Sendtner M, Heinrich PC, Horn F: Association of transcription factor APRF and protein kinase Jak1 with the interleukin-6 signal transducer gp130. Science 263:89, 1994
85. Stahl N, Boulton TG, Farruggella T, Ip NY, Davis S, Witthuhn BA, Quelle FW, Silvennoinen O, Barbieri G, Pellegrini S, Ihle JN, Yancopoulos GD: Association and activation of Jak-Tyk kinases by CNTF-LIF-OSM-IL-6β receptor components. Science 263:92, 1994
86. Narazaki M, Witthuhn BA, Yoshida K, Silvennoinen O, Yasukawa K, Ihle JN, Kishimoto T, Taga T: Activation of JAK2 kinase mediated by the interleukin 6 signal transducer gp130. Proc Natl Acad Sci USA 91:2285, 1994
87. Quelle FW, Sato N, Witthuhn BA, Inhorn RC, Eder M, Miyajima A, Griffin JD, Ihele JN: JAK2 associates with the βc chain of the receptor for granulocyte-macrophage colony-stimulating factor, and its activation requires the membrane-proximal region. Mol Cell Biol 14:4335, 1994
88. Johnston JA, Kawamura M, Kirken RA, Chen Y-Q, Blake TB, Shibuya K, Ortaldo JR, McVicar DW, O'Shea JJ: Phosphorylation and activation of the Jak-3 Janus kinase in response to interleukin-2. Nature 370:151, 1994
89. Kirken RA, Rui H, Malabarba MG, Farrar WL: Identification of interleukin-2 receptor-associated tyrosine kinase p116 as novel leukocyte-specific Janus kinase. J Biol Chem 269:19136, 1994
90. Tanaka N, Asao H, Ohbo K, Ishii N, Takeshita T, Nakamura M, Sasaki H, Sugamura K: Physical association of JAK1 and JAK2 tyrosine kinases with the interleukin-2 receptor β and γ chains. Proc Natl Acad Sci USA 91:7271, 1994
91. Stahl N, Farruggella J, Boulton TG, Zhong Z, Darnell JE, Yancopoulos GD: Modular tyrosine-based motifs in cytokine receptors specify choice of STATs and other substrates. Science 267:1349, 1995
92. Darnell JE Jr, Kerr IM, Stark GR: Jak-STAT pathways and transcriptional activation in response to IFNs and other extracellular signaling proteins. Science 264:1415, 1994
93. Baumann H, Prowse KR, Marinkovic S, Won KA, Jahreis GP: Stimulation of hepatic acute phase response by cytokines and glucocorticoids. Ann NY Acad Sci 557:280, 1989
94. Akira S, Kishimoto T: IL-6 and NF-IL6 in acute-phase response and viral infection. Immunol Rev 127:25, 1992
95. Wegenka UM, Bushmann J, Lütticken C, Heinrich PC, Horn F: Acute-phase response factor, a nuclear factor binding to acute-phae response elements, is rapidly activated by interleukin-6 at the posttranslational level. Mol Cell Biol 13:276, 1993
96. Akira S, Nishio Y, Inoue M, Wang XJ, Wei S, Matsusaka T, Yoshida K, Sudo T, Naruto M, Kishimoto T: Molecular cloning of APRF, a novel IFN-stimulated gene factor 3 p91-related transcription factor involved in the gp130-mediated signaling pathway. Cell 77:63, 1994
97. Zhong Z, Wen Z, Darnell JE Jr: Stat 3: A new family member that is activated through tyrosine phosphorylation in response to EGF and IL-6. Science 264:95, 1994
98. Tian S-S, Lamb P, Seidel HM, Stein RB, Rosen J: Rapid activation of the STAT3 transcription factor by granulocyte colony-stimulating factor. Blood 84:1760, 1994
99. Isshiki H, Akira S, Tanabe O, Nakajima T, Shimamoto T, Hirano T, Kishimoto T: Constitutive and IL-1 inducible factors interact with the IL-1 responsive element in the IL-6 gene. Mol Cell Biol 10:2757, 1990
100. Akira S, Isshiki H, Sugita T, Tanabe O, Kinoshita S, Nishio Y, Nakajima T, Hirano T, Kishimoto T: A nuclear factor for IL-6 expression (NF-IL6) is a member of a C/EBP family. EMBO J 9:1897, 1990
101. Birkenmeier EH, Gwynn B, Howard S, Jerry J, Gordon JI, Landschulz WH, McKnight SL: Tissue-specific expression, developmental regulation, and genetic mapping of the gene encoding CCAAT/enhancer binding protein. Genes Dev 3:1146, 1989
102. Isshiki H, Akira S, Sugita T, Nishio Y, Hashimoto S, Pawlowski T, Suematsu S, Kishimoto T: Reciprocal expression of NF-IL6 and C/EBP in hepatocyte: Possible involvement of NF-IL6 in acute phase protein gene expression. New Biol 3:63, 1991
103. Natsuka S, Akira S, Sugita T, Hashimoto S, Nishio Y, Isshiki H, Kishimoto T: Macrophage differentiation specific expression of NF-IL6, a transcription factor for IL-6. Blood 79:460, 1992
104. Poli V, Mancini FP, Cortese R: IL-6DBP, a nuclear protein involved in interleukin-6 signal transduction, defines a new family of leucine zipper proteins related to C/EBP. Cell 63:643, 1990
105. Nakajima T, Kinoshita S, Sasagawa T, Sasaki K, Naruto M, Kishimoto T, Akira S: Phosphorylation at threonine-235 by a ras-dependent mitogen-activated protein kinase cascade is essential for transcription factor NF-IL6. Proc Natl Acad Sci USA 90:2207, 1993
106. Tanaka T, Akira S, Yoshida K, Umemoto M, Yoneda Y, Shirafuji N, Fujiwara H, Suematsu S, Yoshida N, Kishimoto T: Targeted disruption of the NF-IL6 gene discloses its essential role in bacteria killing and tumor cytotoxicity by macrophages. Cell 80:353, 1995
107. Screpanti I, Romani L, Musiani P, Modesti A, Fattori E, Lazzaro D, Sellito C, Scarpa S, Bellavia D, Lattanzio G, Bistoni F, Frati L, Cortese R, Gulino A, Ciliberto G, Costantini F, Poli V: Lymphoproliferative disorder and imbalanced T-helper response in C/EBPβ-deficient mice. EMBO J 14:1932, 1995
108. Kinoshita S, Akira S, Kishimoto T: A member of the C/ EBP family, NF-IL6β, forms a heterodimer and transcriptionally synergizes with NF-IL6. Proc Natl Acad Sci USA 87:1473, 1992
109. Roman C, Platero JS, Shuman J, Calame K: Ig/EBP-1: A ubiquitously expressed immunoglobulin enhancer binding protein that is similar to C/EBP and heterodimerizes with C/EBP. Genes Dev 4:1404, 1990
110. Nathan CF, Hibbs JM: Role of nitric oxide synthesis in macrophage antimicrobial activity. Curr Opin Immunol 3:65, 1991
111. Jilka RL, Hangoc G, Girasole G, Passeri G, Williams DC, Abrams JS, Boyce B, Broxmeyer H, Manolagas SC: Increased osteoclast development after estrogen loss: Mediation by interleukin-6. Science 257:88, 1992
112. Poli V, Balena R, Fattori E, Markatos A, Yamamoto M, Tanaka H, Ciliberto G, Rodan GA, Costantini F: Interleukin-6 deficient mice are protected from bone loss caused by estrogen depletion. EMBO J 13:1189, 1994
113. Tamura T, Udagawa N, Takahashi N, Miyaura C, Tanaka S, Koishihara Y, Saito H, Yamada Y, Ohsugi Y, Ohkawa H, Nanjyo M, Kumaki K, Kishimoto T, Suda T: Soluble interleukin-6 receptor triggers osteoclast formation by interleukin-6. Proc Natl Acad Sci USA 90:11924, 1993
114. Gaillard JP, Bataille R, Brailly H, Zuber C, Yasukawa K, Altai M, Maruo N, Taga T, Kishimoto T, Klein B: Increased and highly stable levels of functional soluble interleukin-6 receptor in sera of patients with monoclonal gammopathy. Eur J Immunol 23:820, 1993
115. De Benedetti F, Massa M, Pignatti P, Albani S, Novick D, Martini A: Serum soluble interleukin 6 (IL-6) receptor and IL-6/ soluble IL-6 receptor complex in systemic juvenile rheumatoid arthritis. J Clin Invest 93:2114, 1994
116. Sui X, Tsuji K, Tanaka R, Tajima S, Muraoka K, Ebihara Y, Ikebuchi K, Yasukawa K, Taga T, Kishimoto T, Nakahata T: gp130 and c-kit signallings synergize ex vivo expansion of human primitive hemopoietic progenitor cells. Proc Natl Acad Sci USA 92:2859, 1995