The Anti-Inflammatory Effects of the Small Molecule Pifithrin-μ on BV2 Microglia

Developmental Neuroscience

Volumn 37, Issue 4-5, 2015, Pages 363-375

  Fleiss, Bobbi ^a,b,c,d   Chhor, Vibol ^a,b,c,d   Rajudin, Nazurah ^a   Lebon, Sophie ^b,c,d   Hagberg, Henrik ^a,e   Gressens, Pierre ^a,b,c,d   Thornton, Claire ^a  

^a ST THOMAS HOSPITAL   (United Kingdom)

^b U1141   (United States)

^c UNIVERSITÉ PARIS DESCARTES   (France)

^d PremUP   (France)

^e UNIVERSITY OF GOTHENBURG   (Sweden)

Author keywords

2 phenylethynesulfonamide; Neuroinflammation; Neuroprotective; Phenotype; Pifithrin

Indexed keywords

ANTIINFLAMMATORY AGENT; CYCLOOXYGENASE 2; HEAT SHOCK PROTEIN 70; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; INTERLEUKIN 4; NEUROPROTECTIVE AGENT; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA COACTIVATOR 1ALPHA; PIFITHRIN MU; PROTEIN BCL 2; PROTEIN P53; SMALL INTERFERING RNA; UNCLASSIFIED DRUG; BENZOTHIAZOLE DERIVATIVE; PIFITHRIN; TOLUENE;

ANIMAL CELL; ANTIINFLAMMATORY ACTIVITY; ARTICLE; CELL LYSATE; CELL VIABILITY ASSAY; CYTOKINE PRODUCTION; GENE EXPRESSION; GENE SILENCING; GLYCOLYSIS; METABOLISM; MICROGLIA; MITOCHONDRION; MOUSE; MTT ASSAY; NEUROPROTECTION; NONHUMAN; PHAGOCYTOSIS; PHENOTYPE; PRIORITY JOURNAL; PROTEIN BINDING; REAL TIME POLYMERASE CHAIN REACTION; WESTERN BLOTTING; ANALOGS AND DERIVATIVES; ANIMAL; ANTAGONISTS AND INHIBITORS; CELL LINE; DRUG EFFECTS; IMMUNOLOGY; INFLAMMATION;

ANIMALS; BENZOTHIAZOLES; CELL LINE; GENE EXPRESSION; INFLAMMATION; MICE; MICROGLIA; MITOCHONDRIA; NEUROPROTECTIVE AGENTS; TOLUENE; TUMOR SUPPRESSOR PROTEIN P53;

EID: 84938200868     PISSN: 03785866     EISSN: 14219859     Source Type: Journal    
DOI: 10.1159/000370031     Document Type: Article

References (66)

1. Schafer DP, Lehrman EK, Kautzman AG, Koyama R, Mardinly AR, Yamasaki R, Ranso-hoff RM, Greenberg ME, Barres BA, Stevens B: Microglia sculpt postnatal neural circuits in an activity and complement-dependent manner. Neuron 2012; 74:691-705.
2. Basson MA, Wingate RJ: Congenital hypopla-sia of the cerebellum: developmental causes and behavioral consequences. Front Neuro-anat 2013; 7:29.
3. Edwards, A. D, Brocklehurst, P, Gunn, A. J, Halliday, H, Juszczak, E, Levene, M, Strohm B, Thoresen M, Whitelaw A, Azzopardi D: Neurological outcomes at 18 months of age after moderate hypothermia for perinatal hy-poxic ischaemic encephalopathy: synthesis and meta-analysis of trial data. BMJ 2010; 340:c363.
4. Thornton C, Rousset CI, Kichev A, Miyakuni Y, Vontell R, Baburamani AA, Fleiss B, Gres-sens P, Hagberg H: Molecular mechanisms of neonatal brain injury. Neurol Res Int 2012; 2012:506320.
5. Cilio MR, Ferriero DM: Synergistic neuro-protective therapies with hypothermia. Semin Fetal Neonatal Med 2010; 15:293-298.
6. Faulkner S, Bainbridge A, Kato T, Chan-drasekaran M, Kapetanakis AB, Hristova M, Liu M, Evans S, De Vita E, Kelen D, Sanders RD, Edwards AD, Maze M, Cady EB, Raivich G, Robertson NJ: Xenon-augmented hypothermia reduces early lactate/N-acetylaspar-tate and cell death in perinatal asphyxia. Ann Neurol 2011; 70:133-150.
7. Bac P, Maurois P, Dupont C, Pages N, Stables JP, Gressens P, Evrard P, Vamecq J: Magnesium deficiency-dependent audiogenic seizures (MDDASs) in adult mice: a nutritional model for discriminatory screening of anti-convulsant drugs and original assessment of neuroprotection properties. J Neurosci 1998; 18:4363-4373.
8. Robertson NJ, Faulkner S, Fleiss B, Bain-bridge A, Andorka C, Price D, Powell E, Lecky-Thompson L, Thei L, Chandrasekaran M, Hristova M, Cady EB, Gressens P, Golay X, Raivich G: Melatonin augments hypother-mic neuroprotection in a perinatal asphyxia model. Brain 2013; 136:90-105.
9. Dahmani S, Rouelle D, Gressens P, Mantz J: Effects of dexmedetomidine on hippocampal focal adhesion kinase tyrosine phosphorylation in physiologic and ischemic conditions. Anesthesiology 2005; 103:969-977.
10. Nelson KB, Dambrosia JM, Grether JK, Phillips TM: Neonatal cytokines and coagulation factors in children with cerebral palsy. Ann Neurol 1998; 44:665-675.
11. Aly H, Khashaba MT, El-Ayouty M, El-Sayed O, Hasanein BM: IL-1β, IL-6 and TNF-α and outcomes of neonatal hypoxic ischemic en-cephalopathy. Brain Dev 2006; 28:178-182.
12. Grabrucker AM: Environmental factors in autism. Front Psychiatry 2012; 3:118.
13. Rakic P: Neuron-glia relationship during granule cell migration in developing cerebel-lar cortex. A Golgi and electronmicroscopic study in Macacus Rhesus. J Comp Neurol 1971; 141:283-312.
14. Steele AJ, Prentice AG, Hoffbrand AV, Yo-gashangary BC, Hart SM, Lowdell MW, Samuel ER, North JM, Nacheva EP, Chanalaris A, Kottaridis P, Cwynarski K, Wickremasinghe RG: 2-Phenylacetylenesulfonamide (PAS) induces p53-independent apoptotic killing of B-chronic lymphocytic leukemia (CLL) cells. Blood 2009; 114:1217-1225.
15. Leu JI, Pimkina J, Frank A, Murphy ME, George DL: A small molecule inhibitor of in-ducible heat shock protein 70. Mol Cell 2009; 36:15-27.
16. Kannan S, Saadani-Makki F, Muzik O, Chakraborty P, Mangner TJ, Janisse J, Romero R, Chugani DC: Microglial activation in perinatal rabbit brain induced by intrauterine inflammation: detection with 11C-(R)-PK11195 and small-animal PET. J Nucl Med 2007; 48:946-954.
17. Chung K, Wallace J, Kim SY, Kalyanasunda-ram S, Andalman AS, Davidson TJ, Mirz-abekov JJ, Zalocusky KA, Mattis J, Denisin AK, Pak S, Bernstein H, Ramakrishnan C, Grosenick L, Gradinaru V, Deisseroth K: Structural and molecular interrogation of intact biological systems. Nature 2013; 497:332-337.
18. Lenroot RK, Yeung PK: Heterogeneity within autism spectrum disorders: what have we learned from neuroimaging studies? Front Hum Neurosci 2013; 7:733.
19. Block ML, Zecca L, Hong JS: Microglia-me-diated neurotoxicity: uncovering the molecular mechanisms. Nat Rev Neurosci 2007; 8: 57-69.
20. Hagberg H, Mallard C: Effect of inflammation on central nervous system development and vulnerability. Curr Opin Neurol 2005; 18: 117-123.
21. Faustino JV, Wang X, Johnson CE, Klibanov A, Derugin N, Wendland MF, Vexler ZS: Mi-croglial cells contribute to endogenous brain defenses after acute neonatal focal stroke. J Neurosci 2011; 31:12992-13001.
22. Kigerl KA, Gensel JC, Ankeny DP, Alexander JK, Donnelly DJ, Popovich PG: Identification of two distinct macrophage subsets with divergent effects causing either neurotoxicity or regeneration in the injured mouse spinal cord. J Neurosci 2009; 29:13435-13444.
23. Colton CA: Heterogeneity of microglial activation in the innate immune response in the brain. J Neuroimmune Pharmacol 2009; 4: 399-418.
24. Ransohoff RM, Perry VH: Microglial physiology: unique stimuli, specialized responses. Annu Rev Immunol 2009; 27:119-145.
25. Chhor V, Le Charpentier T, Lebon S, Ore MV, Celador IL, Josserand J, Degos V, Jacotot E, Hagberg H, Savman K, Mallard C, Gressens P, Fleiss B: Characterization of phenotype markers and neuronotoxic potential of polarised primary microglia in vitro. Brain Behav Immun 2013; 32:70-85.
26. Lund S, Christensen KV, Hedtjarn M, Mortensen AL, Hagberg H, Falsig J, Hassel-dam H, Schrattenholz A, Porzgen P, Leist M: The dynamics of the LPS triggered inflammatory response of murine microglia under different culture and in vivo conditions. J Neu-roimmunol 2006; 180:71-87.
27. Michelucci A, Heurtaux T, Grandbarbe L, Morga E, Heuschling P: Characterization of the microglial phenotype under specific pro-inflammatory and anti-inflammatory conditions: effects of oligomeric and fibrillar amyloid-β. J Neuroimmunol 2009; 210:3-12.
28. Henn A, Lund S, Hedtjarn M, Schrattenholz A, Porzgen P, Leist M: The suitability of BV2 cells as alternative model system for primary microglia cultures or for animal experiments examining brain inflammation. ALTEX 2009; 26:83-94.
29. Mitchell RH, Goldstein BI: Inflammation in children and adolescents with neuropsychiat-ric disorders: a systematic review. J Am Acad Child Adolesc Psychiatry 2014; 53:274-296.
30. Kaindl AM, Degos V, Peineau S, Gouadon E, Chhor V, Loron G, Le Charpentier T, Josserand J, Ali C, Vivien D, Collingridge GL, Lombet A, Issa L, Rene F, Loeffler JP, Kave-laars A, Verney C, Mantz J, Gressens P: Activation of microglial N-methyl-D-aspartate receptors triggers inflammation and neuronal cell death in the developing and mature brain. Ann. Neurol 2012; 72:536-549.
31. Takeuchi H, Jin S, Wang J, Zhang G, Kawa-nokuchi J, Kuno R, Sonobe Y, Mizuno T, Su-zumura A: Tumor necrosis factor-alpha induces neurotoxicity via glutamate release from hemichannels of activated microglia in an autocrine manner. J Biol Chem 2006; 281: 21362-21368.
32. Butovsky O, Ziv Y, Schwartz A, Landa G, Tal-palar AE, Pluchino S, Martino G, Schwartz M: Microglia activated by IL-4 or IFN-γ differentially induce neurogenesis and oligodendro-genesis from adult stem/progenitor cells. Mol Cell Neurosci 2006; 31:149-160.
33. Ezzati M, Broad K, Kawano G, Faulkner S, Hassell J, Fleiss B, Gressens P, Fierens I, Ros-tami J, Maze M, Sleigh JW, Anderson B, Sanders RD, Robertson NJ: Pharmacokinetics of dexmedetomidine combined with therapeutic hypothermia in a piglet asphyxia model. Acta Anaesthesiol Scand 2014; 58:733-742.
34. Fleiss B, Nilsson MK, Blomgren K, Mallard C: Neuroprotection by the histone deacetylase inhibitor trichostatin A in a model of lipo-polysaccharide-sensitised neonatal hypoxic-ischaemic brain injury. J Neuroinflammation 2012; 9:70.
35. Mantovani A, Sica A, Sozzani S, Allavena P, Vecchi A, Locati M: The chemokine system in diverse forms of macrophage activation and polarization. Trends Immunol 2004; 25:677-686.
36. Martinez FO, Helming L, Gordon S: Alternative activation of macrophages: an immuno-logic functional perspective. Annu Rev Immunol 2009; 27:451-483.
37. Haldipur P, Dupuis N, Degos V, Moniaux N, Chhor V, Rasika S, Schwendiman L, Le Char-pentier T, Rougier E, Amouyal P, Amouyal G, Dournaud P, Bréchot C, El Ghouzzi V, Faivre J, Fleiss B, Mani S, Gressens P: HIP/PAP prevents excitotoxic neuronal death and promotes plasticity. Ann Clin Transl Neurol 2014; 1:739-754.
38. Wright S, Hacohen Y, Jacobson L, Agrwal S, Gupta R, Philip S, Smith M, Lim M, Wassmer E, Vincent A: N-methyl-D-aspartate receptor antibody (NMDAR-Ab) mediated neurological disease-results of a UK-based surveillance study in children. Arch Dis Child, in press.
39. Favrais G, Schwendimann L, Gressens P, Le-lievre V: Cyclooxygenase-2 mediates the sensitizing effects of systemic IL-1-β on excito-toxic brain lesions in newborn mice. Neurobiol Dis 2007; 25:496-505.
40. Harding DR, Humphries SE, Whitelaw A, Marlow N, Montgomery HE: Cognitive outcome and cyclo-oxygenase-2 gene (-765 G/C) variation in the preterm infant. Arch Dis Child Fetal Neonatal Ed 2007; 92:F108-F112.
41. Leu JI, Pimkina J, Frank A, Murphy ME, George DL: A small molecule inhibitor of in-ducible heat shock protein 70. Mol Cell 2009; 36:15-27.
42. Green DR, Chipuk JE: p53 and metabolism: inside the TIGAR. Cell 2006; 126:30-32.
43. Garden GA, Guo W, Jayadev S, Tun C, Bal-caitis S, Choi J, Montine TJ, Moller T, Morrison RS: HIV associated neurodegeneration requires p53 in neurons and microglia. FASEB J 2004; 18:1141-1143.
44. Jayadev S, Nesser NK, Hopkins S, Myers SJ, Case A, Lee RJ, Seaburg LA, Uo T, Murphy SP, Morrison RS, Garden GA: Transcription factor p53 influences microglial activation phenotype. Glia 2011; 59:1402-1413.
45. Silverman JL, Yang M, Lord C, Crawley JN: Behavioural phenotyping assays for mouse models of autism. Nat Rev Neurosci 2010; 11: 490-502.
46. Titulaer MJ, McCracken L, Gabilondo I, Ar-mangue T, Glaser C, Iizuka T, Honig LS, Benseler SM, Kawachi I, Martinez-Hernandez E, Aguilar E, Gresa-Arribas N, Ryan-Flo-rance N, Torrents A, Saiz A, Rosenfeld MR, Balice-Gordon R, Graus F, Dalmau J: Treatment and prognostic factors for long-term outcome in patients with anti-NMDA receptor encephalitis: an observational cohort study. Lancet Neurol 2013; 12:157-165.
47. Depino AM: Peripheral and central inflammation in autism spectrum disorders. Mol Cell Neurosci 2013; 53:69-76.
48. Kotani N, Hashimoto H, Sessler DI, Yasuda T, Ebina T, Muraoka M, Matsuki A: Expression of genes for proinflammatory cytokines in alveolar macrophages during propofol and isoflurane anesthesia. Anesth Analg 1999; 89: 1250-1256.
49. Rosenfeld MR, Dalmau J: Anti-NMDA-re-ceptor encephalitis and other synaptic autoimmune disorders. Curr Treat Options Neu-rol 2011; 13:324-332.
50. Leypoldt F, Titulaer MJ, Aguilar E, Walther J, Bonstrup M, Havemeister S, Teegen B, Lutge-hetmann M, Rosenkranz M, Magnus T, Dal-mau J: Herpes simplex virus-1 encephalitis can trigger anti-NMDA receptor encephalitis: case report. Neurology 2013; 81:1637-1639.
51. Hagerman R, Hoem G, Hagerman P: Fragile X and autism: intertwined at the molecular level leading to targeted treatments. Mol Autism 2010; 1:12.
52. Nishimura Y, Martin CL, Vazquez-Lopez A, Spence SJ, Alvarez-Retuerto AI, Sigman M, Steindler C, Pellegrini S, Schanen NC, Warren ST, Geschwind DH: Genome-wide expression profiling of lymphoblastoid cell lines distinguishes different forms of autism and reveals shared pathways. Hum Mol Genet 2007; 16:1682-1698.
53. O'Neill LA, Kaltschmidt C: NF-κB: a crucial transcription factor for glial and neuronal cell function. Trends Neurosci 1997; 20: 252-258.
54. Hagberg H, Mallard C, Rousset CI, Xiaoyang W: Apoptotic mechanisms in the immature brain: involvement of mitochondria. J Child Neurol 2009; 24:1141-1146.
55. Wang X, Leverin AL, Han W, Zhu C, Johansson BR, Jacotot E, Ten VS, Sims NR, Hagberg H: Isolation of brain mitochondria from neonatal mice. J Neurochem 2011; 119:1253-1261.
56. Wang X, Stridh L, Li W, Dean J, Elmgren A, Gan L, Eriksson K, Hagberg H, Mallard C: Li-popolysaccharide sensitizes neonatal hypoxic-ischemic brain injury in a MyD88-dependent manner. J Immunol 2009; 183:7471-7477.
57. Bona E, Andersson AL, Blomgren K, Gilland E, Puka-Sundvall M, Gustafson K, Hagberg H: Chemokine and inflammatory cell response to hypoxia-ischemia in immature rats. Pediatr Res 1999; 45:500-509.
58. McRae A, Gilland E, Bona E, Hagberg H: Mi-croglia activation after neonatal hypoxic-ischemia. Brain Res Dev Brain Res 1995; 84: 245-252.
59. Butovsky O, Jedrychowski MP, Moore CS, Cialic R, Lanser AJ, Gabriely G, Koeglsperger T, Dake B, Wu PM, Doykan CE, Fanek Z, Liu L, Chen Z, Rothstein JD, Ransohoff RM, Gygi SP, Antel JP, Weiner HL: Identification of a unique TGF-β-dependent molecular and functional signature in microglia. Nat Neurosci 2014; 17:131-143.
60. Seubert CN, Zhu W, Pavlinec C, Gravenstein N, Martynyuk AE: Developmental effects of neonatal isoflurane and sevoflurane exposure in rats. Anesthesiology 2013; 119:358-364.
61. Kargaran P, Lenglet S, Montecucco F, Mach F, Copin JC, Vutskits L: Impact of propofol anaesthesia on cytokine expression profiles in the developing rat brain: an experimental study. Eur J Anaesthesiol 2014, Epub ahead of print.
62. Vincent A, Irani SR, Lang B: Potentially pathogenic autoantibodies associated with epilepsy and encephalitis in children and adults. Epilepsia 2011; 52(suppl 8):8-11.
63. Granerod J, Cousens S, Davies NW, Crow-croft NS, Thomas SL: New estimates of incidence of encephalitis in England. Emerg Infect Dis 2013; 19:1455-1462.
64. Lobritto SJ, Rosenthal P, Bouw R, Leung M, Snell P, Mamelok RD: Pharmacokinetics of mycophenolate mofetil in stable pediatric liver transplant recipients receiving mycophe-nolate mofetil and cyclosporine. Liver Transpl 2007; 13:1570-1575.
65. Hayder S, Lafolie P, Bjork O, Ahstrom L, Peterson C: 6-Mercaptopurine in cerebrospinal fluid during oral maintenance therapy of children with acute lymphoblastic leukemia. Med Oncol Tumor Pharmacother 1988; 5: 187-189.
66. Hofacer RD, Deng M, Ward CG, Joseph B, Hughes EA, Jiang C, Danzer SC, Loepke AW: Cell age-specific vulnerability of neurons to anesthetic toxicity. Ann Neurol 2013; 73:695-704.