A panoramic review and in silico analysis of IL-11 structure and function

Cytokine and Growth Factor Reviews

Volumn 32, Issue , 2016, Pages 41-61

  Negahdaripour, Manica ^a,b   Nezafat, Navid ^a   Ghasemi, Younes ^a,b,c  

^a SHIRAZ UNIVERSITY OF MEDICAL SCIENCES   (Iran)

^b SHIRAZ UNIVERSITY OF MEDICAL SCIENCES   (Iran)

^c SHIRAZ UNIVERSITY OF MEDICAL SCIENCES   (Iran)

Author keywords

Cancer; Cytokine; GP 130; Inflammation; Interleukin 11; Interleukin 6

Indexed keywords

GLYCOPROTEIN GP 130; HYPOXIA INDUCIBLE FACTOR 1ALPHA; INTERLEUKIN 11; INTERLEUKIN 11 RECEPTOR ALPHA; INTERLEUKIN 6; OPRELVEKIN; RECOMBINANT INTERLEUKIN 11; STAT3 PROTEIN; TRANSCRIPTION FACTOR; TRANSCRIPTION FACTOR AP1; UNCLASSIFIED DRUG;

ANTIINFLAMMATORY ACTIVITY; BREAST CANCER; CANCER GROWTH; CANCER ONSET; CANCER PROGNOSIS; CANCER SURVIVAL; CARCINOGENESIS; CELL DAMAGE; COMPUTER MODEL; CYTOKINE PRODUCTION; DISEASE PREDISPOSITION; GASTROINTESTINAL CARCINOMA; GENERAL ASPECTS OF DISEASE; HEMATOPOIESIS; HISTORY OF MEDICINE; HUMAN; IMMUNOMODULATION; METASTASIS; MUCOSAL DISEASE; MUCOSAL INJURY; MULTIPLE SCLEROSIS; NIDATION; NONHUMAN; PREGNANCY; PRIORITY JOURNAL; PROTEIN ANALYSIS; PROTEIN CONFORMATION; PROTEIN FUNCTION; PROTEIN PROTEIN INTERACTION; PROTEIN STRUCTURE; REVIEW; SEQUENCE ALIGNMENT; SIGNAL TRANSDUCTION; SPINAL CORD INJURY; STRUCTURE ACTIVITY RELATION; STRUCTURE ANALYSIS; THROMBOCYTOPENIA; ANIMAL; ANTAGONISTS AND INHIBITORS; CHEMICAL STRUCTURE; CHEMISTRY; COMPUTER SIMULATION; IMMUNOLOGY; METABOLISM;

ANIMALS; COMPUTER SIMULATION; HUMANS; INTERLEUKIN-11; MOLECULAR STRUCTURE; SIGNAL TRANSDUCTION;

EID: 85006321440     PISSN: 13596101     EISSN: 18790305     Source Type: Journal    
DOI: 10.1016/j.cytogfr.2016.06.002     Document Type: Review

References (156)

1. [1] Paul, S.R., Bennett, F., Calvetti, J.A., Kelleher, K., Wood, C.R., O'hara, R.M.J., et al. Molecular cloning of a cDNA encoding interleukin 11, a stromal cell-derived lymphopoietic and hematopoietic cytokine. Proc. Natl. Acad. Sci. U. S. A. 87 (1990), 7512–7516.
2. [2] Kaye, J.A., FDA licensure of NEUMEGA to prevent severe chemotherapy-induced thrombocytopenia. Stem Cells 16:Suppl. 2 (1998), 207–223.
3. [3] Dorner, A.J., Goldman, S.J., Keith, J.C. Jr., Interleukin-11. BioDrugs 8 (1997), 418–429.
4. [4] Keith, J.C. Jr, Chapter 15 – interleukin-11 A2 – thomson AW. Lotze MT. The Cytokine Handbook (Fourth Edition), 2003, Academic Press, London, 363–381.
5. [5] Dembic, Z., Chapter 6 – cytokines of the immune system: interleukins. The Cytokines of the Immune System, 2015, Academic Press, Amsterdam, 143–239.
6. [6] Du, X.X., Williams, D.A., IL11: review of molecular, cell biology, and clinical use. Blood 89 (1997), 3897–3908.
7. [7] Tan, H., Dan, G., Gong, H., Cao, L., Purification and characterization of recombinant truncated human interleukin-11 expressed as fusion protein in escherichia coli. Biotechnol. Lett. 27 (2005), 905–910.
8. [8] Montazeri-Najafabady, N., Ghasemi, Y., Mobasher, M.A., Ghasemian, A., Rasoul-Amini, S., Ebrahimi Codon, S., Optimization, cloning and expression of interleukin 11 in two different E. coli systems. Appl. Microbiol. 7 (2013), 2717–2722.
9. [9] McKinley, D., Wu, Q., Yang-Feng, T., Yang, Y.-C., Genomic sequence and chromosomal location of human interleukin-11 gene (IL11). Genomics 13 (1992), 814–819.
10. [10] Yin, T., Yang, Y.C., Mitogen-activated protein kinases and ribosomal S6 protein kinases are involved in signaling pathways shared by interleukin-11, interleukin-6, leukemia inhibitory factor, and oncostatin M in mouse 3T3-L1 cells. J. Biol. Chem. 269 (1994), 3731–3738.
11. [11] Lebeau, B.T., Montero Julian, F.A., Wijdenes, J., Müller-Newen, G., Dahmen, H., Chérel, M., et al. Reconstitution of two isoforms of the human interleukin-11 receptor and comparison of their functional properties. FEBS Lett. 407 (1997), 141–147.
12. [12] Barton, V.A., Hudson, K.R., Heath, J.K., Identification of three distinct receptor binding sites of murine interleukin-11. J. Biol. Chem. 274 (1999), 5755–5761.
13. [13] Kanehisa, M., Sato, Y., Kawashima, M., Furumichi, M., Tanabe, M., KEGG as a reference resource for gene and protein annotation. Nucleic Acids Res. 44 (2016), D457–62.
14. [14] Johnstone, C.N., Chand, A., Putoczki, T.L., Ernst, M., Emerging roles for IL-11 signaling in cancer development and progression: focus on breast cancer. Cytokine Growth Factor Rev. 26 (2015), 489–498.
15. [15] Putoczki, T.L., Dobson, R.C.J., Griffin, M.D.W., The structure of human interleukin-11 reveals receptor-binding site features and structural differences from interleukin-6. Acta Cryst. D70 (2014), 2277–2285.
16. [16] Garbers, C., Scheller, J., Interleukin-6 and interleukin-11. Same same but different. Biol. Chem. 394 (2013), 1145–1161.
17. [17] Di Tommaso, P., Moretti, S., Xenarios, I., Orobitg, M., Montanyola, A., Chang, J.M., et al. T-Coffee: a web server for the multiple sequence alignment of protein and RNA sequences using structural information and homology extension. Nucleic Acids Res. 39 (2011), W13–7.
18. [18] Waterhouse, A.M., Procter, J.B., Martin, D.M.A., Clamp, M., Barton GJ. Jalview Version 2—a multiple sequence alignment editor and analysis workbench. Bioinformatics 25 (2009), 1189–1191.
19. [19] Czupryn, M.J., McCoy, J.M., Scoble, H.A., Structure-function relationships in human interleukin-11. J. Biol. Chem. 270 (1995), 978–985.
20. [20] Putoczki, T., Ernst, M., More than a sidekick: the IL-6 family cytokine IL-11 links inflammation to cancer. J. Leukoc. Biol. 88 (2010), 1109–1117.
21. [21] Griffin, M.D.W., Ernst, M., Putoczki, T., The structure of human interleukin-11 reveals features of biological significance. Cytokine, 63, 2013, 267.
22. [22] Kenley, R.A., Warne, N.W., Acid-Catalyzed-Peptide-Bond-Hydrolysis-of-Recombinant-Human-Interleukin-11. Pharm. Res. 11 (1994), 72–76.
23. [23] Jung, Y., Ahn, H., Kim, D.-S., Hwang, Y.R., Ho, S.-H., Kim, D.-S., et al. Improvement of biological and pharmacokinetic features of human interleukin-11 by site-directed mutagenesis. Biochem. Biophys. Res. Commun. 405 (2011), 399–404.
24. [24] Huising, M.O., Kruiswijk, C.P., van Schijndel, J.E., Savelkoul, H.F., Flik, G., Verburg-van Kemenade BM. Multiple and highly divergent IL-11 genes in teleost fish. Immunogenetics 57 (2005), 432–443.
25. [25] UniProt, C., UniProt: a hub for protein information. Nucleic Acids Res. 43 (2015), D204–12.
26. [26] Tamura, K., Stecher, G., Peterson, D., Filipski, A., Kumar, S., MEGA6: molecular evolutionary genetics analysis version 6. 0. Mol. Biol. Evol. 30 (2013), 2725–2729.
27. [27] Czupryn, M., Bennett, F., Dube, J., Grant, K., Scoble, H., Sookdeo, H., et al. Alanine-scanning mutagenesis of human interleukin-11: identifcation of regions important for biological activity. Ann. N. Y. Acad. Sci. 21 (1995), 152–164.
28. [28] Putoczki, T.L., Ernst, M., IL-11 signaling as a therapeutic target for cancer. Immunotherapy 7 (2015), 441–453.
29. [29] Ernst, M., Najdovska, M., Grail, D., Lundgren-May, T., Buchert, M., Tye, H., et al. STAT3 and STAT1 mediate IL-11-dependent and inflammation-associated gastric tumorigenesis in gp130 receptor mutant mice. J. Clin. Invest. 118 (2008), 1727–1738.
30. [30] Grotzinger, J., Kurapkat, G., Wollmer, A., Kalai, M., Rose-John, S., The family of the IL-6-type cytokines: specificity and promiscuity of the receptor complexes. Proteins 27 (1997), 96–109.
31. [31] Tacken, I., Dahmen, H., Boisteau, O., Minvielle, S., Jacques, Y., Grötzinger, J., et al. Definition of receptor binding sites on human interleukin-11 by molecular modeling-guided mutagenesis. Eur. J. Biochem. 265 (1999), 645–655.
32. [32] Harmegnies, D., Wang, X.M., Vandenbussche, P., Leon, A., Vusio, P., Grotzinger, J., et al. Characterization of a potent human interleukin-11 agonist. Biochem. J. 375 (2003), 23–32.
33. [33] Underhill-Day, N., McGovern, L.A., Karpovich, N., Mardon, H.J., Barton, V.A., Heath, J.K., Functional characterization of W147A: a high-affinity interleukin-11 antagonist. Endocrinology 144 (2003), 3406–3414.
34. [34] Lee, C.G., Hartl, D., Matsuura, H., Dunlop, F.M., Scotney, P.D., Fabri, L.J., et al. Endogenous IL-11 signaling is essential in Th2- and IL-13-induced inflammation and mucus production. Am. J. Respir. Cell Mol. Biol. 39 (2008), 739–746.
35. [35] Finn, R.D., Mistry, J., Tate, J., Coggill, P., Heger, A., Pollington, J.E., Gavin, O.L., Gunasekaran Ceric, G., Forslund, K., Holm, L., Sonnhammer, E.L.L., Eddy, S.R., Bateman, A., The Pfam protein families database. Nucleic Acids Res., 2014, D222–D230.
36. [36] Schultz, J., Milpetz, F., Bork, P., Ponting, C.P., SMART, a simple modular architecture research tool: identification of signaling domains. Proc. Natl. Acad. Sci. U. S. A. 95 (1998), 5857–5864.
37. [37] Letunic, I., Doerks, T., Bork, P., SMART: recent updates, new developments and status in 2015. Nucleic Acids Res. 43 (2015), D257–D260.
38. [38] Sigrist, C.J., de Castro, E., Cerutti, L., Cuche, B.A., Hulo, N., Bridge, A., et al. New and continuing developments at PROSITE. Nucleic Acids Res. 41 (2013), D344–7.
39. [39] Dosztányi, Z., Csizmók, V., Tompa, P., Simon, I., IUPred: web server for the prediction of intrinsically unstructured regions of proteins based on estimated energy content. Bioinformatics 21 (2005), 3433–3434.
40. [40] Coletta, A., Pinney, J.W., Solis, D.Y., Marsh, J., Pettifer, S.R., Attwood, T.K., Low-complexity regions within protein sequences have position-dependent roles. BMC Syst. Biol., 4, 2010, 43.
41. [41] Dunker, A.K., Lawson, J.D., Brown, C.J., Williams, R.M., Romero, P., Oh, J.S., et al. Intrinsically disordered protein. J. Mol. Graph. Model. 19 (2001), 26–59.
42. [42] Dosztányi, Z., Mészáros, B., Simon, I., ANCHOR: web server for predicting protein binding regions in disordered proteins. Bioinformatics 25 (2009), 2745–2746.
43. [43] Bamba, S., Andoh, A., Yasui, H., Makino, J., Kim, S., Fujiyama, Y., Regulation of IL-11 expression in intestinal myofibroblasts: role of c-Jun AP-1- and MAPK-dependent pathways. Am. J. Physiol. Gastrointest. Liver Physiol. 285 (2003), G529–38.
44. [44] Szklarczyk, D., Franceschini, A., Wyder, S., Forslund, K., Heller, D., Huerta-Cepas, J., et al. STRING v10: protein–protein interaction networks, integrated over the tree of life. Nucleic Acids Res. 43 (2015), D447–52.
45. [45] Balakrishnan, L., Soman, S., Patil, Y.B., Advani, J., Thomas, J.K., Desai, D.V., et al. IL-11/IL11RA receptor mediated signaling: a web accessible knowledgebase. Cell Commun. Adhes. 20 (2013), 81–86.
46. [46] Schwertschlag, U.S., Trepicchio, W.L., Dykstra, K.H., Keith, J.C., Turner, K.J., Dorner, A.J., Hematopoietic, immunomodulatory and epithelial effects of interleukin-11. Leukemia 13 (1999), 1307–1315.
47. [47] Tang, S., Chen, H., Zhang, Z., Structured models for recombinant human interleukin-11 fermentation. Biochem. Eng. J. 35 (2007), 210–217.
48. [48] Léon, A., Wang, X.M., Champion-Arnaud, P., Sobczyk, A., Pain, B., Content, J., et al. Expression of a bioactive recombinant human interleukin-11 in chicken HD11 cell line. Cytokine 30:6 (2005), 382–390.
49. [49] Musashi, M., Yang, Y.C., Paul, S.R., Clark, S.C., Sudo, T., Ogawa, M., Direct and synergistic effects of interleukin 11 on murine hemopoiesis in culture. Proc. Natl. Acad. Sci. U. S. A. 88 (1991), 765–769.
50. [50] Grivennikov, S.I., IL-11: a prominent pro-tumorigenic member of the IL-6 family. Cancer Cell 24 (2013), 145–147.
51. [51] Hemmann, U., Gerhartz, C., Heesel, B., Sasse, J., Kurapkat, G., Grötzinger, J., et al. Differential activation of acute phase response Factor/Stat3 and stat1 via the cytoplasmic domain of the interleukin 6 signal transducer gp130: II. src homology SH2 domains define the specificty of STAT factor activation. J. Biol. Chem. 271 (1996), 12999–13007.
52. [52] Heinrich, P.C., Behrmann, I., Haan, S., Hermanns, H.M., Muller-Newen, G., Schaper, F., Principles of interleukin (IL)-6-type cytokine signalling and its regulation. Biochem. J. 374 (2003), 1–20.
53. [53] Ernst, M., Putoczki, T.L., Molecular pathways: IL11 as a tumor-promoting cytokine-translational implications for cancers. Clin. Cancer Res. 20 (2014), 5579–5588.
54. [54] Tebbutt, N.C., Giraud, A.S., Inglese, M., Jenkins, B., Waring, P., Clay, F.J., et al. Reciprocal regulation of gastrointestinal homeostasis by SHP2 and STAT-mediated trefoil gene activation in gp130 mutant mice. Nat. Med. 8 (2002), 1089–1097.
55. [55] Gough, D.J., Corlett, A., Schlessinger, K., Wegrzyn, J., Larner, A.C., Levy, D.E., Mitochondrial STAT3 supports ras-dependent oncogenic transformation. Science 324 (2009), 1713–1716.
56. [56] Taga, T., Kishimoto, T., Gp130 and the interleukin-6 family of cytokines. J. Cell. Physiol. 15 (1997), 797–819.
57. [57] Silver, J.S., Hunter CA. gp130 at the nexus of inflammation, autoimmunity, and cancer. J. Leukoc. Biol. 88 (2010), 1145–1156.
58. [58] Cherel, M., Sorel, M., Lebeau, B., Dubois, S., Moreau, J.F., Bataille, R., et al. Molecular cloning of two isoforms of a receptor for the human hematopoietic cytokine interleukin-11. Blood 86 (1995), 2534–2540.
59. [59] Davidson, A.J., Freeman, S.A., Crosier, K.E., Wood, C.R., Crosier, P.S., Expression of murine interleukin 11 and its receptor α‐Chain in adult and embryonic tissues. Stem Cells 15 (1997), 119–124.
60. [60] Romas, E., Udagawa, N., Zhou, H., Tamura, T., Saito, M., Taga, T., et al. The role of gp130-mediated signals in osteoclast development: regulation of interleukin 11 production by osteoblasts and distribution of its receptor in bone marrow cultures. J. Exp. Med. 183 (1996), 2581–2591.
61. [61] Robb, L., Hilton, D.J., Brook-Carter, P.T., Begley, C.G., Identification of a second murine interleukin-11 receptor alpha-chain gene (IL11Ra2) with a restricted pattern of expression. Genomics 40 (1997), 387–394.
62. [62] Nieminen, P., Morgan, N.V., Fenwick, A.L., Parmanen, S., Veistinen, L., Mikkola, M.L., et al. Inactivation of IL11 signaling causes craniosynostosis, delayed tooth eruption, and supernumerary teeth. Am. J. Hum. Genet. 89 (2011), 67–81.
63. [63] Papadopoulos, J.S., Agarwala, R., COBALT: constraint-based alignment tool for multiple protein sequences. Bioinformatics 23 (2007), 1073–1079.
64. [64] Bowman, T., Garcia, R., Turkson, J., Jove, R., STATs in oncogenesis. Oncogene 19 (2000), 2474–2488.
65. [65] Bromberg, J., Stat proteins and oncogenesis. J. Clin. Invest. 109 (2002), 1139–1142.
66. [66] Ernst, M., Putoczki, T.L., Targeting IL-11 signaling in colon cancer. Oncotarget 4 (2013), 1860–1861.
67. [67] Kortylewski, M., Kujawski, M., Wang, T., Wei, S., Zhang, S., Pilon-Thomas, S., et al. Inhibiting Stat3 signaling in the hematopoietic system elicits multicomponent antitumor immunity. Nat. Med. 11 (2005), 1314–1321.
68. [68] Elias, J.A., Tang, W., Horowitz, M.C., Cytokine and hormonal stimulation of human osteosarcoma interleukin-11 production. Endocrinology 136 (1995), 489–498.
69. [69] Du, X., Everett, E.T., Wang, G., Lee, W.H., Yang, Z., Williams, D.A., Murine interleukin-11 (IL-11) is expressed at high levels in the hippocampus and expression is developmentally regulated in the testis. J. Cell. Physiol. 168 (1996), 362–372.
70. [70] Hill, G.R., Cooke, K.R., Teshima, T., Crawford, J.M., Keith, J.C. Jr., Brinson, Y.S., et al. Interleukin-11 promotes T cell polarization and prevents acute graft-versus-host disease after allogeneic bone marrow transplantation. J. Clin. Invest. 102 (1998), 115–123.
71. [71] Howlett, M., Chalinor, H.V., Buzzelli, J.N., Nguyen, N., van Driel, I.R., Bell, K.M., et al. IL-11 is a parietal cell cytokine that induces atrophic gastritis. Gut 61 (2012), 1398–1409.
72. [72] Weich, N.S., Wang, A., Fitzgerald, M., Neben, T.Y., Donaldson, D., Giannotti, J., et al. Recombinant human interleukin-11 directly promotes megakaryocytopoiesis In vitro. Blood 90 (1997), 3893–3902.
73. [73] Tepler, I., Elias, L., Smith, J.W. 2nd, Hussein, M., Rosen, G., Chang, A.Y., et al. A randomized placebo-controlled trial of recombinant human interleukin-11 in cancer patients with severe thrombocytopenia due to chemotherapy. Blood 87 (1996), 3607–3614.
74. [74] Gordon, M.S., McCaskill-Stevens, W.J., Battiato, L.A., Loewy, J., Loesch, D., Breeden, E., et al. A phase I trial of recombinant human interleukin-11 (neumega rhIL-11 growth factor) in women with breast cancer receiving chemotherapy. Blood 87 (1996), 3615–3624.
75. [75] Aribi, A., Kantarjian, H., Koller, C., Thomas, D., Faderl, S., Garcia-Manero, G., et al. The effect of interleukin 11 on thrombocytopenia associated with tyrosine kinase inhibitor therapy in patients with chronic myeloid leukemia. Cancer 113 (2008), 1338–1343.
76. [76] Tsimberidou, A.M., Giles, F.J., Khouri, I., Bueso-Ramos, C., Pilat, S., Thomas, D.A., et al. Low-dose interleukin-11 in patients with bone marrow failure: update of the M.D. Anderson Cancer Center experience. Ann. Oncol. 16 (2005), 139–145.
77. [77] Montero, A.J., Estrov, Z., Freireich, E.J., Khouri, I.F., Koller, C.A., Kurzrock, R., Phase II study of low-dose interleukin-11 in patients with myelodysplastic syndrome. Leuk. Lymphoma 47 (2006), 2049–2054.
78. [78] Wu, S., Zhang, Y., Xu, L., Dai, Y., Teng, Y., Ma, S., et al. Multicenter, randomized study of genetically modified recombinant human interleukin-11 to prevent chemotherapy-induced thrombocytopenia in cancer patients receiving chemotherapy. Support. Care Cancer 20 (2012), 1875–1884.
79. [79] De Haan, G., Dontje, B., Engel, C., Loeffler, M., Nijhof, W., In vivo effects of interleukin-11 and stem cell factor in combination with erythropoietin in the regulation of erythropoiesis. Br. J. Haematol. 90 (1995), 783–790.
80. [80] Denis, C.V., Kwack, K., Saffaripour, S., Maganti, S., Andre, P., Schaub, R.G., et al. Interleukin 11 significantly increases plasma von Willebrand factor and factor VIII in wild type and von Willebrand disease mouse models. Blood 97 (2001), 465–472.
81. [81] Martuscelli, G., Fiorellini, J.P., Crohin, C.C., Howell, T.H., The effect of interleukin-11 on the progression of ligature-induced periodontal disease in the beagle dog. J. Periodontol. 71 (2000), 573–578.
82. [82] Shaker, O.G., Ghallab, N.A., IL-17 and IL-11 GCF levels in aggressive and chronic periodontitis patients: relation to PCR bacterial detection. Mediators Inflamm., 2012, 2012, 174764.
83. [83] Zhang, X., Putoczki, T., Markovic-Plese, S., IL-11 in multiple sclerosis. Oncotarget 6:32 (2015), 32297–32298.
84. [84] Shaikh, P.Z., Cytokines & their physiologic and pharmacologic functions in inflammation: a review. Int. J. Pharm. Life Sci. 2 (2011), 1247–1263.
85. [85] Trepicchio, W.L., Wang, L., Bozza, M., Dorner, A.J., IL-11 regulates macrophage effector function through the inhibition of nuclear factor-kappaB. J. Immunol. 159 (1997), 5661–5670.
86. [86] Bozza, M., Bliss, J.L., Dorner, A.J., Trepicchio, W.L., Interleukin-11 modulates Th1/Th2 cytokine production from activated CD4+ T cells. J. Interferon Cytokine Res. 21 (2001), 21–30.
87. [87] Chen, Q., Rabach, L., Noble, P., Zheng, T., Lee, C.G., Homer, R.J., et al. IL-11 receptor alpha in the pathogenesis of IL-13-induced inflammation and remodeling. J. Immunol. 174 (2005), 2305–2313.
88. [88] Yin, T.G., Schendel, P., Yang, Y.C., Enhancement of in vitro and in vivo antigen-specific antibody responses by interleukin 11. J. Exp. Med. 175 (1992), 211–216.
89. [89] Ain, R., Trinh, M.L., Soares, M.J., Interleukin-11 signaling is required for the differentiation of natural killer cells at the maternal-fetal interface. Dev. Dyn. 231 (2004), 700–708.
90. [90] Mahboubi, K., Biedermann, B.C., Carroll, J.M., Pober, J.S., IL-11 activates human endothelial cells to resist immune-mediated injury. J. Immunol. 164 (2000), 3837–3846.
91. [91] Opal, S.M., Keith, J.C., Palardy, J.E., Parejo, N., Recombinant human interleukin-11 has anti-inflammatory actions yet does not exacerbate systemic listeria infection. J. Infect. Dis. 181 (2000), 754–756.
92. [92] Moreland, L., Gugliotti, R., King, K., Chase, W., Weisman, M., Greco, T., et al. Results of a phase-I/II randomized, masked, placebo-controlled trial of recombinant human interleukin-11 (rhIL-11) in the treatment of subjects with active rheumatoid arthritis. Arthritis Res. 3 (2001), 247–252.
93. [93] Sands, B.E., Winston, B.D., Salzberg, B., Safdi, M., Barish, C., Wruble, L., et al. Randomized, controlled trial of recombinant human interleukin-11 in patients with active Crohn's disease. Aliment. Pharmacol. Ther. 16 (2002), 399–406.
94. [94] Bussel, J.B., Mukherjee, R., Stone, A.J., A pilot study of rhuIL-11 treatment of refractory ITP. Am. J. Hematol. 66 (2001), 172–177.
95. [95] Yucel, O.O., Berker, E., Gariboglu, S., Otlu, H., Interleukin-11, interleukin-1beta, interleukin-12 and the pathogenesis of inflammatory periodontal diseases. J. Clin. Periodontol. 35 (2008), 365–370.
96. [96] Burnett, A.F., Biju, P.G., Lui, H., Hauer-Jensen, M., Oral interleukin 11 as a countermeasure to lethal total-body irradiation in a murine model. Radiat. Res. 180 (2013), 595–602.
97. [97] Yang, L., Wang, R., Gao, Y., Xu, X., Fu, K., Wang, S., et al. The protective role of interleukin-11 against neutron radiation injury in mouse intestines via MEK/ERK and PI3K/Akt dependent pathways. Dig. Dis. Sci. 59 (2014), 1406–1414.
98. [98] Orazi, A., Du, X., Yang, Z., Kashai, M., Williams, D.A., Interleukin-11 prevents apoptosis and accelerates recovery of small intestinal mucosa in mice treated with combined chemotherapy and radiation. Lab. Invest. 75 (1996), 33–42.
99. [99] Du, X., Liu, Q., Yang, Z., Orazi, A., Rescorla, F.J., Grosfeld, J.L., et al. Protective effects of interleukin-11 in a murine model of ischemic bowel necrosis. Am. J. Physiol. 272 (1997), G545–G552.
100. [100] Chang, M., Williams, A., Ishizawa, L., Knoppel, A., van de Ven, C., Cairo, M.S., Endogenous interleukin-11 (IL-11) expression is increased and prophylactic use of exogenous IL-11 enhances platelet recovery and improves survival during thrombocytopenia associated with experimental group B streptococcal sepsis in neonatal rats. Blood Cells Mol. Dis. 22 (1996), 57–67.
101. [101] Hendry, J.H., Potten, C.S., Chadwick, C., Bianchi, M., Cell death (apoptosis) in the mouse small intestine after low doses: effects of dose-rate, 14.7 MeV neutrons, and 600 MeV (maximum energy) neutrons. Int. J. Radiat. Biol. Relat. Stud. Phys. Chem. Med. 42 (1982), 611–620.
102. [102] Ropeleski, M.J., Tang, J., Walsh-Reitz, M.M., Musch, M.W., Chang, E.B., Interleukin-11-induced heat shock protein 25 confers intestinal epithelial-specific cytoprotection from oxidant stress. Gastroenterology 124 (2003), 1358–1368.
103. [103] Opal, S.M., Jhung, J.W., Keith, J.C. Jr., Goldman, S.J., Palardy, J.E., Parejo, N.A., Additive effects of human recombinant interleukin-11 and granulocyte colony-stimulating factor in experimental gram-negative sepsis. Blood 93 (1999), 3467–3472.
104. [104] Maeshima, K., Takahashi, T., Nakahira, K., Shimizu, H., Fujii, H., Katayama, H., et al. A protective role of interleukin 11 on hepatic injury in acute endotoxemia. Shock 21 (2004), 134–138.
105. [105] Obana, M., Miyamoto, K., Murasawa, S., Iwakura, T., Hayama, A., Yamashita, T., et al. Therapeutic administration of IL-11 exhibits the postconditioning effects against ischemia-reperfusion injury via STAT3 in the heart. Am. J. Physiol. Heart Circ. Physiol. 303 (2012), H569–77.
106. [106] Maier, R., Ganu, V., Lotz, M., Interleukin-11, an inducible cytokine in human articular chondrocytes and synoviocytes, stimulates the production of the tissue inhibitor of metalloproteinases. J. Biol. Chem. 268 (1993), 21527–21532.
107. [107] Sands, B.E., Bank, S., Sninsky, C.A., Robinson, M., Katz, S., Singleton, J.W., et al. Preliminary evaluation of safety and activity of recombinant human interleukin 11 in patients with active Crohn's disease. Gastroenterology 117 (1999), 58–64.
108. [108] Antin, J.H., Lee, S.J., Neuberg, D., Alyea, E., Soiffer, R.J., Sonis, S., et al. A phase I/II double-blind, placebo-controlled study of recombinant human interleukin-11 for mucositis and acute GVHD prevention in allogeneic stem cell transplantation. Bone Marrow Transplant. 29 (2002), 373–377.
109. [109] Ghalib, R., Levine, C., Hassan, M., McClelland, T., Goss, J., Stribling, R., et al. Recombinant human interleukin-11 improves thrombocytopenia in patients with cirrhosis. Hepatology 37 (2003), 1165–1171.
110. [110] Lawitz, E.J., Hepburn, M.J., Casey, T.J., A pilot study of interleukin-11 in subjects with chronic hepatitis C and advanced liver disease nonresponsive to antiviral therapy. Am. J. Gastroenterol. 99 (2004), 2359–2364.
111. [111] Kiessling, S., Muller-Newen, G., Leeb, S.N., Hausmann, M., Rath, H.C., Strater, J., et al. Functional expression of the interleukin-11 receptor α-chain and evidence of antiapoptotic effects in human colonic epithelial cells. J. Biol. Chem. 279 (2004), 10304–10315.
112. [112] Boerma, M., Wang, J., Burnett, A.F., Santin, A.D., Roman, J.J., Hauer-Jensen, M., Local administration of interleukin-11 ameliorates intestinal radiation injury in rats. Cancer Res. 67 (2007), 9501–9506.
113. [113] Potten, C.S., Protection of the small intestinal clonogenic stem cells from radiation-induced damage by pretreatment with interleukin 11 also increases murine survival time. Stem Cells 14 (1996), 452–459.
114. [114] Furugaki, K., Moriya, Y., Iwai, T., Yorozu, K., Yanagisawa, M., Kondoh, K., et al. Erlotinib inhibits osteolytic bone invasion of human non-small-cell lung cancer cell line NCI-H292. Clin. Exp. Metastasis 28 (2011), 649–659.
115. [115] Luis-Ravelo, D., Anton, I., Zandueta, C., Valencia, K., Ormazabal, C., Martinez-Canarias, S., et al. A gene signature of bone metastatic colonization sensitizes for tumor-induced osteolysis and predicts survival in lung cancer. Oncogene 33 (2014), 5090–5099.
116. [116] Morinaga, Y., Fujita, N., Ohishi, K., Zhang, Y., Tsuruo, T., Suppression of interleukin-11-mediated bone resorption by cyclooxygenases inhibitors. J. Cell. Physiol. 175 (1998), 247–254.
117. [117] Xiang, Z.L., Zeng, Z.C., Fan, J., Tang, Z.Y., Zeng, H.Y., Expression of connective tissue growth factor and interleukin-11 in intratumoral tissue is associated with poor survival after curative resection of hepatocellular carcinoma. Mol. Biol. Rep. 39 (2012), 6001–6006.
118. [118] Necula, L.G., Chivu-Economescu, M., Stanciulescu, E.L., Bleotu, C., Dima, S.O., Alexiu, I., et al. IL-6 and IL-11 as markers for tumor aggressiveness and prognosis in gastric adenocarcinoma patients without mutations in Gp130 subunits. J. Gastrointestin. Liver Dis. 21 (2012), 23–29.
119. [119] Ren, C., Chen, Y., Han, C., Fu, D., Chen, H., Plasma interleukin-11 (IL-11) levels have diagnostic and prognostic roles in patients with pancreatic cancer. Tumour Biol. 35 (2014), 11467–11472.
120. [120] Pan, D., Xu, L., Liu, H., Zhang, W., Liu, W., Liu, Y., et al. High expression of interleukin-11 is an independent indicator of poor prognosis in clear-cell renal cell carcinoma. Cancer Sci. 106 (2015), 592–597.
121. [121] Győrffy, B., Surowiak, P., Budczies, J., Lánczky, A., Online survival analysis software to assess the prognostic value of biomarkers using transcriptomic data in non-Small-Cell lung cancer. PLoS One, 8, 2013, e82241.
122. [122] Louria-Hayon, I., Frelin, C., Ruston, J., Gish, G., Jin, J., Kofler, M.M., et al. Lnk adaptor suppresses radiation resistance and radiation-induced B-cell malignancies by inhibiting IL-11 signaling. Proc. Natl. Acad. Sci. U. S. A. 110 (2013), 20599–20604.
123. [123] Jung, J.E., Lee, H.G., Cho, I.H., Chung, D.H., Yoon, S.H., Yang, Y.M., et al. STAT3 is a potential modulator of HIF-1-mediated VEGF expression in human renal carcinoma cells. FASEB J. 19 (2005), 1296–1298.
124. [124] Onnis, B., Fer, N., Rapisarda, A., Perez, V.S., Melillo, G., Autocrine production of IL-11 mediates tumorigenicity in hypoxic cancer cells. J. Clin. Invest. 123 (2013), 1615–1629.
125. [125] Bockhorn, J., Dalton, R., Nwachukwu, C., Huang, S., Prat, A., Yee, K., et al. MicroRNA-30c inhibits human breast tumour chemotherapy resistance by regulating TWF1 and IL-11. Nat. Commun., 4, 2013, 1393.
126. [126] Chua, A.C., Klopcic, B.R., Ho, D.S., Fu, S.K., Forrest, C.H., Croft, K.D., et al. Dietary iron enhances colonic inflammation and IL-6/IL-11-Stat3 signaling promoting colonic tumor development in mice. PLoS One, 8, 2013, e78850.
127. [127] Huber, S., Gagliani, N., Zenewicz, L.A., Huber, F.J., Bosurgi, L., Hu, B., et al. IL-22BP is regulated by the inflammasome and modulates tumorigenesis in the intestine. Nature 491 (2012), 259–263.
128. [128] Thiem, S., Pierce, T.P., Palmieri, M., Putoczki, T.L., Buchert, M., Preaudet, A., et al. mTORC1 inhibition restricts inflammation-associated gastrointestinal tumorigenesis in mice. J. Clin. Invest. 123 (2013), 767–781.
129. [129] Schaper, F., Rose-John, S., Interleukin-6: Biology, signaling and strategies of blockade. Cytokine Growth Factor Rev. 26 (2015), 475–487.
130. [130] Calon, A., Espinet, E., Palomo-Ponce, S., Tauriello, D.V., Iglesias, M., Cespedes, M.V., et al. Dependency of colorectal cancer on a TGF-beta-driven program in stromal cells for metastasis initiation. Cancer Cell 22 (2012), 571–584.
131. [131] Shi, X.Z., Sarna, S.K., Transcriptional regulation of inflammatory mediators secreted by human colonic circular smooth muscle cells. Am. J. Physiol. Gastrointest. Liver Physiol. 289 (2005), G274–84.
132. [132] Torroella-Kouri, M., Keith, J.C., Ivanova, M., Lopez, D.M., IL-11-induced reduction of C/EBP transcription factor binding may contribute to the IL-12 downregulation in tumor-bearing mice. Int. J. Oncol. 22 (2003), 439–448.
133. [133] Jarnicki, A., Putoczki, T., Ernst, M., Stat3: linking inflammation to epithelial cancer—more than a gut feeling?. Cell Div., 5, 2010, 14.
134. [134] Putoczki, T.L., Thiem, S., Loving, A., Busuttil, R.A., Wilson, N.J., Ziegler, P.K., et al. Interleukin-11 is the dominant IL-6 family cytokine during gastrointestinal tumorigenesis and can be targeted therapeutically. Cancer Cell 24 (2013), 257–271.
135. [135] McCoy, E.M., Hong, H., Pruitt, H.C., Feng, X., IL-11 produced by breast cancer cells augments osteoclastogenesis by sustaining the pool of osteoclast progenitor cells. BMC Cancer, 13, 2013, 16.
136. [136] Casimiro, S., Luis, I., Fernandes, A., Pires, R., Pinto, A., Gouveia, A.G., et al. Analysis of a bone metastasis gene expression signature in patients with bone metastasis from solid tumors. Clin. Exp. Metastasis 29 (2012), 155–164.
137. [137] Li, T.M., Wu, C.M., Huang, H.C., Chou, P.C., Fong, Y.C., Tang, C.H., Interleukin-11 increases cell motility and up-regulates intercellular adhesion molecule-1 expression in human chondrosarcoma cells. J. Cell. Biochem. 113 (2012), 3353–3362.
138. [138] Lay, V., Yap, J., Sonderegger, S., Dimitriadis E. Interleukin 11 regulates endometrial cancer cell adhesion and migration via STAT3. Int. J.Oncol. 41 (2012), 759–764.
139. [139] Gupta, J., Robbins, J., Jilling, T., Seth, P., TGFβ-dependent induction of interleukin-11 and interleukin-8 involves SMAD and p38 MAPK pathways in breast tumor models with varied bone metastases potential. Cancer Biol. Ther. 11 (2011), 311–316.
140. [140] Zhou, C., Ji, J., Cai, Q., Shi, M., Chen, X., Yu, Y., et al. MTA2 enhances colony formation and tumor growth of gastric cancer cells through IL-11. BMC Cancer, 15, 2015, 343.
141. [141] Kobayashi, S., Teramura, M., Sugawara, I., Oshimi, K., Mizoguchi, H., Interleukin-11 acts as an autocrine growth factor for human megakaryoblastic cell lines. Blood 81 (1993), 889–893.
142. [142] Baj-Krzyworzeka, M., Majka, M., Pratico, D., Ratajczak, J., Vilaire, G., Kijowski, J., et al. Platelet-derived microparticles stimulate proliferation, survival, adhesion, and chemotaxis of hematopoietic cells. Exp. Hematol. 30 (2002), 450–459.
143. [143] Zhang, Y., Taveggia, C., Melendez-Vasquez, C., Einheber, S., Raine, C.S., Salzer, J.L., et al. Interleukin-11 potentiates oligodendrocyte survival and maturation, and myelin formation. J. Neurosci. 26 (2006), 12174–12185.
144. [144] Zhang, X., Tao, Y., Chopra, M., Dujmovic-Basuroski, I., Jin, J., Tang, Y., et al. IL-11 induces th17 cell responses in patients with early relapsing-Remitting multiple sclerosis. J. Immunol. 194 (2015), 5139–5149.
145. [145] Bilinski, P., Roopenian, D., Gossler, A., Maternal IL-11Ralpha function is required for normal decidua and fetoplacental development in mice. Genes Dev. 12 (1998), 2234–2243.
146. [146] Stewart, C.L., Kaspar, P., Brunet, L.J., Bhatt, H., Gadi, I., Kontgen, F., et al. Blastocyst implantation depends on maternal expression of leukaemia inhibitory factor. Nature 359 (1992), 76–79.
147. [147] Paiva, P., Menkhorst, E., Salamonsen, L., Dimitriadis, E., Leukemia inhibitory factor and interleukin-11: critical regulators in the establishment of pregnancy. Cytokine Growth Factor Rev. 20 (2009), 319–328.
148. [148] Dimitriadis, E., Menkhorst, E., Salamonsen, L.A., Paiva, P., Review: LIF and IL11 in trophoblast-endometrial interactions during the establishment of pregnancy. Placenta 31:Suppl (2010), S99–104.
149. [149] Bao, L., Devi, Y.S., Bowen-Shauver, J., Ferguson-Gottschall, S., Robb, L., Gibori, G., The role of interleukin-11 in pregnancy involves up-regulation of alpha2-macroglobulin gene through janus kinase 2-signal transducer and activator of transcription 3 pathway in the decidua. Mol. Endocrinol. 20 (2006), 3240–3250.
150. [150] Sonderegger, S., Yap, J., Menkhorst, E., Weston, G., Stanton, P.G., Dimitriadis, E., Interleukin (IL)11 mediates protein secretion and modification in human extravillous trophoblasts. Hum. Reprod. 26 (2011), 2841–2849.
151. [151] Cho, N., Nguyen, D.H., Satkunendrarajah, K., Branch, D.R., Fehlings, M.G., Evaluating the role of IL-11, a novel cytokine in the IL-6 family, in a mouse model of spinal cord injury. J. Neuroinflamm., 9, 2012, 134.
152. [152] Xu, S., Neamati, N., gp130: a promising drug target for cancer therapy. Expert Opin. Ther. Targets 17 (2013), 1303–1328.
153. [153] Tefferi, A., JAK inhibitors for myeloproliferative neoplasms: clarifying facts from myths. Blood 119 (2012), 2721–2730.
154. [154] Murphy, G.M. Jr., Bitting, L., Majewska, A., Schmidt, K., Song, Y., Wood, C.R., Expression of interleukin-11 and its encoding mRNA by glioblastoma cells. Neurosci. Lett. 196 (1995), 153–156.
155. [155] Sommer, J., Effenberger, T., Volpi, E., Waetzig, G.H., Bernhardt, M., Suthaus, J., et al. Constitutively active mutant gp130 receptor protein from inflammatory hepatocellular adenoma is inhibited by an anti-gp130 antibody that specifically neutralizes interleukin 11 signaling. J. Biol. Chem. 287 (2012), 13743–13751.
156. [156] Nandurkar, H.H., Robb, L., Tarlinton, D., Barnett, L., Kontgen, F., Begley, C.G., Adult mice with targeted mutation of the interleukin-11 receptor (IL11Ra) display normal hematopoiesis. Blood 90 (1997), 2148–2159.