Astrocytic IL-6 influences the clinical symptoms of EAE in mice

Brain Sciences

Volumn 6, Issue 2, 2016, Pages

  Erta, Maria ^a,b   Giralt, Mercedes ^a,b   Jiménez, Silvia ^a   Molinero, Amalia ^a,b   Comes, Gemma ^a,b   Hidalgo, Juan ^a,b  

^a UNIVERSITAT AUTÒNOMA DE BARCELONA   (Spain)

^b INSTITUT DE NEUROCIÈNCIES   (Spain)

Author keywords

Astrocyte; EAE; Interleukin 6

Indexed keywords

GLIAL FIBRILLARY ACIDIC PROTEIN; INTERLEUKIN 6; LECTIN;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; ASTROCYTE; BODY WEIGHT; CELL INFILTRATION; CLINICAL FEATURE; CONTROLLED STUDY; DEMYELINATION; DISEASE COURSE; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; FEMALE; GENOTYPE; GLIOSIS; GRAY MATTER; HISTOCHEMISTRY; IMMUNOHISTOCHEMISTRY; IMMUNOREACTIVITY; MALE; MORTALITY; MOUSE; NONHUMAN; PARAPLEGIA; REMISSION; WHITE MATTER;

EID: 85009230525     PISSN: None     EISSN: 20763425     Source Type: Journal    
DOI: 10.3390/brainsci6020015     Document Type: Article

References (35)

1. Hirano, T.; Taga, T.; Nakano, N.; Yasukawa, K.; Kashiwamura, S.; Shimizu, K.; Nakajima, K.; Pyun, K.H.; Kishimoto, T. Purification to homogeneity and characterization of human B-cell differentiation factor (BCDF or BSFp-2). Proc. Natl. Acad. Sci. USA 1985, 82, 5490-5494
2. Gruol, D.L.; Nelson, T.E. Physiological and pathological roles of interleukin-6 in the central nervous system. Mol. Neurobiol. 1997, 15, 307-339
3. Schöbitz, B.; de Kloet, E.R.; Sutanto, W.; Holsboer, F. Cellular localization of interleukin 6 mRNA and interleukin 6 receptor mrna in rat brain. Eur. J. Neurosci. 1993, 5, 1426-1435
4. Van Wagoner, N.J.; Benveniste, E.N. Interleukin-6 expression and regulation in astrocytes. J. Neuroimmunol. 1999, 100, 124-139
5. Milo, R.; Kahana, E. Multiple sclerosis: Geoepidemiology, genetics and the environment. Autoimmun. Rev. 2010, 9, A387-A394
6. Baxter, A.G. The origin and application of experimental autoimmune encephalomyelitis. Nat. Rev. Immunol. 2007, 7, 904-912
7. Merrill, J.E.; Benveniste, E.N. Cytokines in inflammatory brain lesions: Helpful and harmful. Trends Neurosci. 1996, 19, 331-338
8. Maimone, D.; Guazzi, G.C.; Annunziata, P. IL-6 detection in multiple sclerosis brain. J. Neurol. Sci. 1997, 146, 59-65
9. Eugster, H.-P.; Frei, K.; Kopf, M.; Lassmann, H.; Fontana, A. IL-6 deficient mice resist myelin oligoden-drocyte glycoprotein-induced autoimmune encephalomyelitis. Eur. J. Immunol. 1998, 28, 2178-2187
10. Mendel, I.; Katz, A.; Kozak, N.; Ben-Nun, A.; Revel, M. Interleukin-6 functions in autoimmune encephalomyelitis: A study in gene-targeted mice. Eur. J. Immunol. 1998, 28, 1727-1737
11. Okuda, Y.; Sakoda, S.; Bernard, C.C.; Fujimura, H.; Saeki, Y.; Kishimoto, T.; Yanagihara, T. IL-6-deficient mice are resistant to the induction of experimental autoimmune encephalomyelitis provoked by myelin oligodendrocyte glycoprotein. Int. Immunol. 1998, 10, 703-708
12. Samoilova, E.B.; Horton, J.L.; Hilliard, B.; Liu, T.S.; Chen, Y. IL-6-deficient mice are resistant to experimental autoimmune encephalomyelitis: Roles of IL-6 in the activation and differentiation of autoreactive T cells. J. Immunol. 1998, 161, 6480-6486
13. Giralt, M.; Ramos, R.; Quintana, A.; Ferrer, B.; Erta, M.; Castro-Freire, M.; Comes, G.; Sanz, E.; Unzeta, M.; Pifarré, P.; et al. Induction of atypical EAE mediated by transgenic production of IL-6 in astrocytes in the absence of systemic IL-6. Glia 2013, 61, 587-600
14. Serada, S.; Fujimoto, M.; Mihara, M.; Koike, N.; Ohsugi, Y.; Nomura, S.; Yoshida, H.; Nishikawa, T.; Terabe, F.; Ohkawara, T.; et al. IL-6 blockade inhibits the induction of myelin antigen-specific Th17 cells and Th1 cells in experimental autoimmune encephalomyelitis. Proc. Natl. Acad. Sci. USA 2008, 105, 9041-9046
15. Spooren, A.; Kolmus, K.; Laureys, G.; Clinckers, R.; De Keyser, J.; Haegeman, G.; Gerlo, S. Interleukin-6, a mental cytokine. Brain Res. Rev. 2011, 67, 157-183
16. Erta, M.; Quintana, A.; Hidalgo, J. Interleukin-6, a major cytokine in the central nervous system. Int. J. Biol. Sci. 2012, 8, 1254-1266
17. Quintana, A.; Erta, M.; Ferrer, B.; Comes, G.; Giralt, M.; Hidalgo, J. Astrocyte-specific deficiency of interleukin-6 and its receptor reveal specific roles in survival, body weight and behavior. Brain Behav. Immun. 2013, 27, 162-173
18. Erta, M.; Giralt, M.; Esposito, F.L.; Fernandez-Gayol, O.; Hidalgo, J. Astrocytic IL-6 mediates locomotor activity, exploration, anxiety, learning and social behavior. Horm. Behav. 2015, 73, 64-74
19. Su, M.; Hu, H.; Lee, Y.; d’Azzo, A.; Messing, A.; Brenner, M. Expression specificity of GFAP transgenes. Neurochem. Res. 2004, 29, 2075-2093
20. Mycko, M.P.; Papoian, R.; Boschert, U.; Raine, C.S.; Selmaj, K.W. Cdna microarray analysis in multiple sclerosis lesions: Detection of genes associated with disease activity. Brain 2003, 126, 1048-1057
21. Lock, C.; Hermans, G.; Pedotti, R.; Brendolan, A.; Schadt, E.; Garren, H.; Langer-Gould, A.; Strober, S.; Cannella, B.; Allard, J.; et al. Gene-microarray analysis of multiple sclerosis lesions yields new targets validated in autoimmune encephalomyelitis. Nat. Med. 2002, 8, 500-508
22. Gijbels, K.; Brocke, S.; Abrams, J.S.; Steinman, L. Administration of neutralizing antibodies to interleukin-6 (IL-6) reduces experimental autoimmune encephalomyelitis and is associated with elevated levels of IL-6 bioactivity in central nervous system and circulation. Mol. Med. 1995, 1, 795-805
23. Willenborg, D.O.; Fordham, S.A.; Cowden, W.B.; Ramshaw, I.A. Cytokines and murine autoimmune encephalomyelitis: Inhibition or enhancement of disease with antibodies to select cytokines, or by delivery of exogenous cytokines using a recombinant vaccinia virus system. Scand. J. Immunol. 1995, 41, 31-41
24. Rodriguez, M.; Pavelko, K.D.; McKinne, C.W.; Leibowitz, J.L. Recombinant human IL-6 suppresses demyelination in a viral model of multiple sclerosis. J. Immunol. 1994, 153, 3811-3821
25. Campbell, I.L.; Abraham, C.R.; Masliah, E.; Kemper, P.; Inglis, J.D.; Oldstone, M.B.A.; Mucke, L. Neurologic disease in transgenic mice by cerebral overexpression of interleukin 6. Proc. Natl. Acad. Sci. USA 1993, 90, 10061-10065
26. Campbell, I.L.; Erta, M.; Lim, S.L.; Frausto, R.; May, U.; Rose-John, S.; Scheller, J.; Hidalgo, J. Trans-signaling is a dominant mechanism for the pathogenic actions of interleukin-6 in the brain. J. Neurosci. 2014, 34, 2503-2513
27. Costantino, C.M.; Baecher-Allan, C.; Hafler, D.A. Multiple sclerosis and regulatory T cells. J. Clin. Immunol. 2008, 28, 697-706
28. Kimura, A.; Kishimoto, T. Il-6: Regulator of Treg/Th17 balance. Eur. J. Immunol. 2010, 40, 1830-1835
29. Murphy, A.C.; Lalor, S.J.; Lynch, M.A.; Mills, K.H. Infiltration of th1 and Th17 cells and activation of microglia in the CNS during the course of experimental autoimmune encephalomyelitis. Brain Behav. Immun. 2010, 24, 641-651
30. Bettelli, E.; Carrier, Y.; Gao, W.; Korn, T.; Strom, T.B.; Oukka, M.; Weiner, H.L.; Kuchroo, V.K. Reciprocal developmental pathways for the generation of pathogenic effector Th17 and regulatory T cells. Nature 2006, 441, 235-238
31. Korn, T.; Mitsdoerffer, M.; Croxford, A.L.; Awasthi, A.; Dardalhon, V.A.; Galileos, G.; Vollmar, P.; Stritesky, G.L.; Kaplan, M.H.; Waisman, A.; et al. IL-6 controls Th17 immunity in vivo by inhibiting the conversion of conventional t cells into Foxp3+ regulatory T cells. Proc. Natl. Acad. Sci. USA 2008, 105, 18460-18465
32. Ma, X.; Reynolds, S.L.; Baker, B.J.; Li, X.; Benveniste, E.N.; Qin, H. IL-17 enhancement of the IL-6 signaling cascade in astrocytes. J. Immunol. 2010, 184, 4898-4906
33. Ogura, H.; Murakami, M.; Okuyama, Y.; Tsuruoka, M.; Kitabayashi, C.; Kanamoto, M.; Nishihara, M.; Iwakura, Y.; Hirano, T. Interleukin-17 promotes autoimmunity by triggering a positive-feedback loop via interleukin-6 induction. Immunity 2008, 29, 628-636
34. Swartz, K.R.; Liu, F.; Sewell, D.; Schochet, T.; Campbell, I.; Sandor, M.; Fabry, Z. Interleukin-6 promotes post-traumatic healing in the central nervous system. Brain Res. 2001, 896, 86-95
35. Fee, D.; Grzybicki, D.; Dobbs, M.; Ihyer, S.; Clotfelter, J.; Macvilay, S.; Hart, M.N.; Sandor, M.; Fabry, Z. Interleukin 6 promotes vasculogenesis of murine brain microvessel endothelial cells. Cytokine 2000, 12, 655-665