IKKβ-mediated inflammatory myeloid cell activation exacerbates experimental autoimmune encephalomyelitis by potentiating Th1/Th17 cell activation and compromising blood brain barrier

Molecular Neurodegeneration

Volumn 11, Issue 1, 2016, Pages

  Lee, Min Jung ^a   Bing, So Jin ^b   Choi, Jonghee ^a   Jang, Minhee ^a   Lee, Gihyun ^a   Lee, Hyunkyoung ^c   Chang, Byung Soo ^d   Jee, Youngheun ^b   Lee, Sung Joong ^c   Cho, Ik Hyun ^a  

^a Kyung Hee University   (South Korea)

^b Jeju National University   (South Korea)

^c Seoul National University   (South Korea)

^d Hanseo University   (South Korea)

Author keywords

Blood brain barrier; Experimental autoimmune encephalomyelitis; IKK conditional deletion; Myeloid cell; T cell

Indexed keywords

CD31 ANTIGEN; CLAUDIN 3; CLAUDIN 5; FC RECEPTOR; FIBRONECTIN; GAMMA INTERFERON; I KAPPA B KINASE BETA; INDUCIBLE NITRIC OXIDE SYNTHASE; INTERLEUKIN 10; INTERLEUKIN 12; INTERLEUKIN 17; INTERLEUKIN 1BETA; INTERLEUKIN 2; INTERLEUKIN 23; INTERLEUKIN 4; INTERLEUKIN 6; PROTEIN ZO1; TRANSCRIPTION FACTOR FOXP3; TRANSFORMING GROWTH FACTOR BETA; TUMOR NECROSIS FACTOR ALPHA; CYTOKINE; I KAPPA B KINASE; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN;

ADULT; ALLERGIC ENCEPHALOMYELITIS; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANTIGEN EXPRESSION; ARTICLE; BLOOD BRAIN BARRIER; BONE MARROW CELL; CELL ACTIVATION; CELL INFILTRATION; CONTROLLED STUDY; FEMALE; GENE DELETION; GENE EXPRESSION REGULATION; IKK BETA GENE; IN VIVO STUDY; LYMPHOCYTE DIFFERENTIATION; LYMPHOCYTE PROLIFERATION; MOUSE; NEUROPATHOLOGY; NONHUMAN; PERITONEUM MACROPHAGE; PROTEIN EXPRESSION; PROTEIN INDUCTION; REGULATORY T LYMPHOCYTE; SIGNAL TRANSDUCTION; T LYMPHOCYTE ACTIVATION; TH1 CELL; TH17 CELL; UPREGULATION; ANIMAL; DRUG EFFECTS; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; IMMUNOLOGY; INFLAMMATION; LYMPHOCYTE ACTIVATION; METABOLISM; PATHOLOGY; TRANSGENIC MOUSE;

ANIMALS; BLOOD-BRAIN BARRIER; CYTOKINES; ENCEPHALOMYELITIS, AUTOIMMUNE, EXPERIMENTAL; I-KAPPA B KINASE; INFLAMMATION; LYMPHOCYTE ACTIVATION; MICE, TRANSGENIC; MYELOID CELLS; NF-KAPPA B; T-LYMPHOCYTES, REGULATORY; TH1 CELLS; TH17 CELLS;

EID: 84979582926     PISSN: None     EISSN: 17501326     Source Type: Journal    
DOI: 10.1186/s13024-016-0116-1     Document Type: Article

References (63)

1. Alvarez JI, Cayrol R, Prat A. Disruption of central nervous system barriers in multiple sclerosis. Biochim Biophys Acta. 2011;1812:252-64.
2. Barnett MH, Prineas JW. Relapsing and remitting multiple sclerosis: pathology of the newly forming lesion. Ann Neurol. 2004;55:458-68.
3. Brambilla R, Dvoriantchikova G, Barakat D, Ivanov D, Bethea JR, Shestopalov VI. Transgenic inhibition of astroglial NF-kappaB protects from optic nerve damage and retinal ganglion cell loss in experimental optic neuritis. J Neuroinflammation. 2012;9:213.
4. Brambilla R, Persaud T, Hu X, Karmally S, Shestopalov VI, Dvoriantchikova G, Ivanov D, Nathanson L, Barnum SR, Bethea JR. Transgenic inhibition of astroglial NF-kappa B improves functional outcome in experimental autoimmune encephalomyelitis by suppressing chronic central nervous system inflammation. J Immunol. 2009;182:2628-40.
5. Brustle A, Brenner D, Knobbe CB, Lang PA, Virtanen C, Hershenfield BM, Reardon C, Lacher SM, Ruland J, Ohashi PS, Mak TW. The NF-kappaB regulator MALT1 determines the encephalitogenic potential of Th17 cells. J Clin Invest. 2012;122:4698-709.
6. Bullard DC, Hu X, Adams JE, Schoeb TR, Barnum SR. p150/95 (CD11c/CD18) expression is required for the development of experimental autoimmune encephalomyelitis. Am J Pathol. 2007;170(6):2001-8.
7. Chen SJ, Wang YL, Fan HC, Lo WT, Wang CC, Sytwu HK. Current status of the immunomodulation and immunomediated therapeutic strategies for multiple sclerosis. Clin Dev Immunol. 2012;2012:970789.
8. (+) T regulatory cells in vivo and enhances their capacity to suppress EAE. Eur J Immunol. 2006;36:2139-49.
9. Cho IH, Hong J, Suh EC, Kim JH, Lee H, Lee JE, Lee S, Kim CH, Kim DW, Jo EK, Lee KE, Karin M, Lee SJ. Role of microglial IKKbeta in kainic acid-induced hippocampal neuronal cell death. Brain. 2008;131:3019-33.
10. Clausen BE, Burkhardt C, Reith W, Renkawitz R, Forster I. Conditional gene targeting in macrophages and granulocytes using LysMcre mice. Transgenic Res. 1999;8:265-77.
11. Dasgupta S, Jana M, Zhou Y, Fung YK, Ghosh S, Pahan K. Antineuroinflammatory effect of NF-kappaB essential modifier-binding domain peptides in the adoptive transfer model of experimental allergic encephalomyelitis. J Immunol. 2004;173:1344-54.
12. El-behi M, Rostami A, Ciric B. Current views on the roles of Th1 and Th17 cells in experimental autoimmune encephalomyelitis. J Neuroimmune Pharmacol. 2010;5:189-97.
13. Ellrichmann G, Thone J, Lee DH, Rupec RA, Gold R, Linker RA. Constitutive activity of NF-kappa B in myeloid cells drives pathogenicity of monocytes and macrophages during autoimmune neuroinflammation. J Neuroinflammation. 2012;9:15.
14. Engelhardt B, Ransohoff RM. Capture, crawl, cross: the T cell code to breach the blood-brain barriers. Trends Immunol. 2012;33:579-89.
15. Flynn KM, Michaud M, Canosa S, Madri JA. CD44 regulates vascular endothelial barrier integrity via a PECAM-1 dependent mechanism. Angiogenesis. 2013a;6:689-705.
16. Flynn KM, Michaud M, Madri JA. CD44 deficiency contributes to enhanced experimental autoimmune encephalomyelitis: a role in immune cells and vascular cells of the blood-brain barrier. Am J Pathol. 2013b;182:1322-36.
17. Ford AL, Foulcher E, Lemckert FA, Sedgwick JD. Microglia induce CD4 T lymphocyte final effector function and death. J Exp Med. 1996;184(5):1737-45.
18. Greten FR, Karin M. The IKK/NF-kappaB activation pathway-a target for prevention and treatment of cancer. Cancer Lett. 2004;206:193-9.
19. Greve B, Weissert R, Hamdi N, Bettelli E, Sobel RA, Coyle A, Kuchroo VK, Rajewsky K, Schmidt-Supprian M. I kappa B kinase 2/beta deficiency controls expansion of autoreactive T cells and suppresses experimental autoimmune encephalomyelitis. J Immuno. 2007;179:179-85.
20. Hendriks JJ, Teunissen CE, de Vries HE, Dijkstra CD. Macrophages and neurodegeneration. Brain Res. 2005;48:185-95.
21. Hilliard B, Samoilova EB, Liu TS, Rostami A, Chen Y. Experimental autoimmune encephalomyelitis in NF-kappa B-deficient mice:roles of NF-kappa B in the activation and differentiation of autoreactive T cells. J Immunol. 1999;163:2937-43.
22. Hohlfeld R. Biotechnological agents for the immunotherapy of multiple sclerosis. Principles, problems and perspectives. Brain. 1997;120(Pt 5):865-916.
23. Hong J, Cho IH, Kwak KI, Suh EC, Seo J, Min HJ, Choi SY, Kim CH, Park SH, Jo EK, Lee S, Lee KE, Lee SJ. Microglial Toll-like receptor 2 contributes to kainic acid-induced glial activation and hippocampal neuronal cell death. J Biol Chem. 2011;285:39447-57.
24. Hwang I, Ha D, Ahn G, Park E, Joo H, Jee Y. Experimental autoimmune encephalomyelitis: association with mutual regulation of RelA (p65)/NF-kappaB and phospho-IkappaB in the CNS. Biochem Biophys Res Commun. 2011;411:464-70.
25. Jang M, Cho IH. Sulforaphane Ameliorates 3-Nitropropionic Acid-Induced Striatal Toxicity by Activating the Keap1-Nrf2-ARE Pathway and Inhibiting the MAPKs and NF-kappaB Pathways. Mol Neurobiol. 2016;53(4):2619-35.
26. Jang M, Lee MJ, Cho IH. Ethyl pyruvate ameliorates 3-nitropropionic acid-induced striatal toxicity through anti-neuronal cell death and anti-inflammatory mechanisms. Brain Behav Immun. 2014;38:151-65.
27. Kalinowska A, Losy J. PECAM-1, a key player in neuroinflammation. Eur J Neurol. 2006;13(12):1284-90.
28. Karin M. The beginning of the end: IkappaB kinase (IKK) and NF-kappaB activation. J Biol Chem. 1999;274:27339-42.
29. Kim H, Ahn M, Choi S, Kim M, Sim KB, Kim J, Moon C, Shin T. Potential role of fibronectin in microglia/macrophage activation following cryoinjury in the rat brain: an immunohistochemical study. Brain Res. 2013;1502:11-9.
30. Landis SC, Amara SG, Asadullah K, Austin CP, Blumenstein R, Bradley EW, et al. A call for transparent reporting to optimize the predictive value of preclinical research. Nature. 2012;490(7419)187-91.
31. Lassmann H, van Horssen J. The molecular basis of neurodegeneration in multiple sclerosis. FEBS Lett. 2011;585:3715-23.
32. Lee DH, Kubera K, Rosenthal B, Kaltschmidt B, Kaltschmidt C, Gold R, Linker RA. Neuronal NF-kappaB ablation does not influence neuro-axonal degeneration in experimental autoimmune demyelination. J Neuroimmunol. 2012;246:38-42.
33. Lee MJ, Jang M, Choi J, Chang BS, Kim DY, Kim SH, Kwak YS, Oh S, Lee JH, Chang BJ, Nah SY, Cho IH. Korean red ginseng and ginsenoside-Rb1/-Rg1 alleviates experimental autoimmune encephalomyelitis by suppressing Th1 and Th17 T cells and upregulating regulatory T cells. Mol Neurobiol. 2016;53(3):1977-2002.
34. Lee MJ, Jang M, Choi J, Lee G, Min HJ, Chung WS, Kim JI, Jee Y, Chae Y, Kim SH, Lee SJ, Cho IH. Bee Venom Acupuncture Alleviates Experimental Autoimmune Encephalomyelitis by Upregulating Regulatory T Cells and Suppressing Th1 and Th17 Responses. Mol Neurobiol. 2016;53(3):1419-45.
35. Linthicum DS. Development of acute autoimmune encephalomyelitis in mice: factors regulating the effector phase of the disease. Immunobiology. 1982;162(3):211-20.
36. Li X, Li TT, Zhang XH, Hou LF, Yang XQ, Zhu FH, Tang W, Zuo JP. Artemisinin analogue SM934 ameliorates murine experimental autoimmune encephalomyelitis through enhancing the expansion and functions of regulatory T cell. PLoS One. 2013;8:e74108.
37. Li ZW, Omori SA, Labuda T, Karin M, Rickert RC. IKK beta is required for peripheral B cell survival and proliferation. J Immunol. 2003;170:4630-7.
38. Liu YM, Liu XJ, Bai SS, Mu LL, Kong QF, Sun B, Wang DD, Wang JH, Shu S, Wang GY, Li HL. The effect of electroacupuncture on T cell responses in rats with experimental autoimmune encephalitis. J Neuroimmunol. 2010;220:25-33.
39. Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 2001;25:402-8.
40. Lu G, Zhang R, Geng S, Peng L, Jayaraman P, Chen C, Xu F, Yang J, Li Q, Zheng H, Shen K, Wang J, Liu X, Wang W, Zheng Z, Qi CF, Si C, He JC, Liu K, Lira SA, Sikora AG, Li L, Xiong H. Myeloid cell-derived inducible nitric oxide synthase suppresses M1 macrophage polarization. Nat Commun. 2015;6:6676.
41. Mc Guire C, Prinz M, Beyaert R, van Loo G. Nuclear factor kappa B (NF-kappaB) in multiple sclerosis pathology. Trends Mol Med. 2013;19:604-13.
42. McFarland HF, Martin R. Multiple sclerosis: a complicated picture of autoimmunity. Nat Immunol. 2007;8:913-9.
43. Mildner A, Mack M, Schmidt H, Brück W, Djukic M, Zabel MD, Hille A, Priller J, Prinz M. CCR2 + Ly-6Chi monocytes are crucial for the effector phase of autoimmunity in the central nervous system. Brain. 2009;132(Pt 9):2487-500.
44. Miron VE. Boyd A, Zhao JW, Yuen TJ, Ruckh JM, Shadrach JL, van Wijngaarden P, Wagers AJ, Williams A, Franklin RJ, ffrench-Constant C. M2 microglia and macrophages drive oligodendrocyte differentiation during CNS remyelination. Nat Neurosci. 2013;16:1211-8.
45. Muzio L, Cavasinni F, Marinaro C, Bergamaschi A, Bergami A, Porcheri C, Cerri F, Dina G, Quattrini A, Cxcl10 enhances blood cells migration in the sub-ventricular zone of mice affected by experimental autoimmune encephalomyelitis. Mol Cell Neurosci. 2010;43(3):268-80.
46. Nam Y, Kim JH, Seo M, Kim JH, Jin M, Jeon S, et al. Lipocalin-2 protein deficiency ameliorates experimental autoimmune encephalomyelitis: the pathogenic role of lipocalin-2 in the central nervous system and peripheral lymphoid tissues. J Biol Chem. 2014;289(24):16773-89.
47. Napoli I, Neumann H. Protective effects of microglia in multiple sclerosis. Exp Neurol. 2010;225:24-8.
48. Nataf S. Neuroinflammation responses and neurodegeneration in multiple sclerosis. Rev Neurol. 2009;165:1023-8.
49. Nickols JC, Valentine W, Kanwal S, Carter BD. Activation of the transcription factor NF-kappaB in Schwann cells is required for peripheral myelin formation. Nat Neurosci. 2003;6:161-7.
50. Okamoto K, Iwai Y, Oh-Hora M, Yamamoto M, Morio T, Aoki K, Ohya K, Jetten AM, Akira S, Muta T, Takayanagi H. IkappaBzeta regulates T(H)17 development by cooperating with ROR nuclear receptors. Nature. 2010;464:1381-5.
51. Ortiz GG, Pacheco-Moises FP, Macias-Islas MA, Flores-Alvarado LJ, Mireles-Ramirez MA, Gonzalez-Renovato ED, et al. Role of the Blood-brain Barrier in Multiple Sclerosis. Arch Med Res. 2014;45:687-97.
52. Pfeiffer F, Schafer J, Lyck R, Makrides V, Brunner S, Schaeren-Wiemers N, Deutsch U, Engelhardt B. Claudin-1 induced sealing of blood-brain barrier tight junctions ameliorates chronic experimental autoimmune encephalomyelitis. Acta Neuropathol. 2011;122(5):601-14.
53. Reddy J, Illes Z, Zhang X, Encinas J, Pyrdol J, Nicholson L, Sobel RA, Wucherpfennig KW, Kuchroo VK. Myelin proteolipid protein-specific CD4 + CD25+ regulatory cells mediate genetic resistance to experimental autoimmune encephalomyelitis. Proc Natl Acad Sci U S A. 2004;101:15434-9.
54. Sedgwick JD, Schwender S, Imrich H, Dorries R, Butcher GW, ter Meulen V. Isolation and direct characterization of resident microglial cells from the normal and inflamed central nervous system. Proc Natl Acad Sci U S A. 1991;88:7438-42.
55. Sica A, Schioppa T, Mantovani A, Allavena P. Tumour-associated macrophages are a distinct M2 polarised population promoting tumour progression: potential targets of anti-cancer therapy. Eur J Cancer. 2006;42:717-27.
56. Takahashi K, Prinz M, Stagi M, Chechneva O, Neumann H. TREM2-transduced myeloid precursors mediate nervous tissue debris clearance and facilitate recovery in an animal model of multiple sclerosis. PLoS Med. 2007;4:e124.
57. van Horssen J, Witte ME, Schreibelt G, de Vries HE. Radical changes in multiple sclerosis pathogenesis. Biochim Biophys Acta. 1812;2011:141-50.
58. Weber MS, Benkhoucha M, Lehmann-Horn K, Hertzenberg D, Sellner J, Santiago-Raber ML, et al. Repetitive pertussis toxin promotes development of regulatory T cells and prevents central nervous system autoimmune disease. PLoS One. 2010;5(12):e16009.
59. Weber MS, Youssef S, Dunn SE, Prod'homme T, Neuhaus O, Stuve O, Greenwood J, Steinman L, Zamvil SS. Statins in the treatment of central nervous system autoimmune disease. J Neuroimmunol. 2006;178:140-8.
60. Willis CL. Glia-induced reversible disruption of blood-brain barrier integrity and neuropathological response of the neurovascular unit. Toxicol Pathol. 2010;39:172-85.
61. Wolburg-Buchholz K, Mack AF, Steiner E, Pfeiffer F, Engelhardt B, Wolburg H. Loss of astrocyte polarity marks blood-brain barrier impairment during experimental autoimmune encephalomyelitis. Acta Neuropathol. 2009;118:219-33.
62. Wraith DC, Nicolson KS, Whitley NT. Regulatory CD4+ T cells and the control of autoimmune disease. Curr Opin Immunol. 2004;16:695-701.
63. Zhu D, Liu M, Yang Y, Ma L, Jiang Y, Zhou L, Huang Q, Pi R, Chen X. Ginsenoside Rd ameliorates experimental autoimmune encephalomyelitis in C57BL/6 mice. J Neurosci Res. 2014;92:1217-26.