Transcriptome sequencing reveals that LPS-triggered transcriptional responses in established microglia BV2 cell lines are poorly representative of primary microglia

Journal of Neuroinflammation

Volumn 13, Issue 1, 2016, Pages

  Das, Amitabh ^a   Kim, Sun Hwa ^a   Arifuzzaman, Sarder ^b   Yoon, Taeho ^a   Chai, Jin Choul ^a   Lee, Young Seek ^a   Park, Kyoung Sun ^a   Jung, Kyoung Hwa ^a   Chai, Young Gyu ^a,b  

^a Hanyang University   (South Korea)

^b Hanyang University   (South Korea)

Author keywords

Gene regulation; Innate immunity; Microglia; RNA sequencing; Transcription factors

Indexed keywords

INTERFERON CONSENSUS SEQUENCE BINDING PROTEIN; INTERFERON REGULATORY FACTOR 2; INTERFERON REGULATORY FACTOR 5; LIPOPOLYSACCHARIDE; PROTEIN KDM1A; PROTEIN NSD3; PROTEIN SETDB2; REGULATOR PROTEIN; RNA; STAT1 PROTEIN; STAT2 PROTEIN; STAT5A PROTEIN; TRANSCRIPTION FACTOR; TRANSCRIPTOME; UNCLASSIFIED DRUG; CYTOKINE; MESSENGER RNA; TLR4 PROTEIN, MOUSE; TOLL LIKE RECEPTOR 4;

ANIMAL CELL; ANIMAL TISSUE; ARTICLE; EPIGENETICS; GENE CLUSTER; MICROGLIA; MOUSE; NEWBORN; NONHUMAN; PROMOTER REGION; PROTEIN MOTIF; QUANTITATIVE ANALYSIS; REAL TIME POLYMERASE CHAIN REACTION; RNA SEQUENCE; RNA TRANSCRIPTION; SEQUENCE ANALYSIS; TRANSCRIPTOMICS; ANALYSIS OF VARIANCE; ANIMAL; BRAIN; CELL CULTURE; CYTOLOGY; DOSE RESPONSE; DRUG EFFECTS; GENE EXPRESSION REGULATION; GENETICS; METABOLISM; PHYSIOLOGY; SIGNAL TRANSDUCTION; TIME FACTOR;

ANALYSIS OF VARIANCE; ANIMALS; ANIMALS, NEWBORN; BRAIN; CELLS, CULTURED; CYTOKINES; DOSE-RESPONSE RELATIONSHIP, DRUG; GENE EXPRESSION REGULATION; LIPOPOLYSACCHARIDES; MICE; MICROGLIA; RNA, MESSENGER; SIGNAL TRANSDUCTION; TIME FACTORS; TOLL-LIKE RECEPTOR 4; TRANSCRIPTION FACTORS; TRANSCRIPTOME;

EID: 84977614161     PISSN: None     EISSN: 17422094     Source Type: Journal    
DOI: 10.1186/s12974-016-0644-1     Document Type: Article

References (69)

1. Streit WJ, Mrak RE, Griffin WS. Microglia and neuroinflammation: a pathological perspective. J Neuroinflammation. 2004;1(1):14.
2. Graeber MB, Streit WJ. Microglia: biology and pathology. Acta Neuropathol. 2010;119(1):89-105.
3. Lawson LJ, Perry VH, Dri P, Gordon S. Heterogeneity in the distribution and morphology of microglia in the normal adult mouse brain. Neuroscience. 1990;39(1):151-70.
4. More SV, Kumar H, Kim IS, Koppulla S, Kim BW, Choi DK. Strategic selection of neuroinflammatory models in Parkinson's disease: evidence from experimental studies. CNS & neurological disorders drug targets. 2013;12(5):680-97.
5. Falsig J, van Beek J, Hermann C, Leist M. Molecular basis for detection of invading pathogens in the brain. J Neurosci Res. 2008;86(7):1434-47.
6. Bodea LG, Wang Y, Linnartz-Gerlach B, Kopatz J, Sinkkonen L, Musgrove R, Kaoma T, Muller A, Vallar L, Di Monte DA et al. Neurodegeneration by activation of the microglial complement-phagosome pathway. The Journal of neuroscience: the official journal of the Society for Neuroscience. 2014;34(25):8546-56.
7. Fan K, Li D, Zhang Y, Han C, Liang J, Hou C, Xiao H, Ikenaka K, Ma J. The induction of neuronal death by up-regulated microglial cathepsin H in LPS-induced neuroinflammation. J Neuroinflammation. 2015;12:54.
8. Bi XL, Yang JY, Dong YX, Wang JM, Cui YH, Ikeshima T, Zhao YQ, Wu CF. Resveratrol inhibits nitric oxide and TNF-alpha production by lipopolysaccharide-activated microglia. Int Immunopharmacol. 2005;5(1):185-93.
9. Lee J, Kim YS, Choi DH, Bang MS, Han TR, Joh TH, Kim SY. Transglutaminase 2 induces nuclear factor-kappaB activation via a novel pathway in BV-2 microglia. J Biol Chem. 2004;279(51):53725-35.
10. 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(2):83-94.
11. Crotti A, Benner C, Kerman BE, Gosselin D, Lagier-Tourenne C, Zuccato C, Cattaneo E, Gage FH, Cleveland DW, Glass CK. Mutant Huntingtin promotes autonomous microglia activation via myeloid lineage-determining factors. Nat Neurosci. 2014;17(4):513-21.
12. Lund S, Porzgen P, Mortensen AL, Hasseldam H, Bozyczko-Coyne D, Morath S, Hartung T, Bianchi M, Ghezzi P, Bsibsi M et al. Inhibition of microglial inflammation by the MLK inhibitor CEP-1347. J Neurochem. 2005;92(6):1439-51.
13. Horvath RJ, Nutile-McMenemy N, Alkaitis MS, Deleo JA. Differential migration, LPS-induced cytokine, chemokine, and NO expression in immortalized BV-2 and HAPI cell lines and primary microglial cultures. J Neurochem. 2008;107(2):557-69.
14. Butovsky O, Jedrychowski MP, Moore CS, Cialic R, Lanser AJ, Gabriely G, Koeglsperger T, Dake B, Wu PM, Doykan CE et al. Identification of a unique TGF-beta-dependent molecular and functional signature in microglia. Nat Neurosci. 2014;17(1):131-43.
15. Stansley B, Post J, Hensley K. A comparative review of cell culture systems for the study of microglial biology in Alzheimer's disease. J Neuroinflammation. 2012;9:115.
16. Lund S, Christensen KV, Hedtjarn M, Mortensen AL, Hagberg H, Falsig J, Hasseldam 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 Neuroimmunol. 2006;180(1-2):71-87.
17. Sultan M, Schulz MH, Richard H, Magen A, Klingenhoff A, Scherf M, Seifert M, Borodina T, Soldatov A, Parkhomchuk D, et al. A global view of gene activity and alternative splicing by deep sequencing of the human transcriptome. Science. 2008;321(5891):956-60.
18. Nagalakshmi U, Wang Z, Waern K, Shou C, Raha D, Gerstein M, Snyder M. The transcriptional landscape of the yeast genome defined by RNA sequencing. Science. 2008;320(5881):1344-9.
19. Witting A, Moller T. Microglia cell culture: a primer for the novice. Methods Mol Biol. 2011;758:49-66.
20. Das A, Chai JC, Kim SH, Park KS, Lee YS, Jung KH, Chai YG. Dual RNA sequencing reveals the expression of unique transcriptomic signatures in lipopolysaccharide-induced BV-2 microglial cells. PLoS One. 2015;10(3):e0121117.
21. Thomas DM, Francescutti-Verbeem DM, Kuhn DM. Gene expression profile of activated microglia under conditions associated with dopamine neuronal damage. FASEB journal: official publication of the Federation of American Societies for Experimental Biology. 2006;20(3):515-7.
22. Bolger AM, Lohse M, Usadel B. Trimmomatic: a flexible trimmer for Illumina sequence data. Bioinformatics. 2014;30(15):2114-20.
23. Dobin A, Davis CA, Schlesinger F, Drenkow J, Zaleski C, Jha S, Batut P, Chaisson M, Gingeras TR. STAR: ultrafast universal RNA-seq aligner. Bioinformatics. 2013;29(1):15-21.
24. Love MI, Huber W, Anders S. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol. 2014;15(12):550.
25. Heinz S, Benner C, Spann N, Bertolino E, Lin YC, Laslo P, Cheng JX, Murre C, Singh H, Glass CK. Simple combinations of lineage-determining transcription factors prime cis-regulatory elements required for macrophage and B cell identities. Mol Cell. 2010;38(4):576-89.
26. Jung KH, Das A, Chai JC, Kim SH, Morya N, Park KS, Lee YS, Chai YG. RNA sequencing reveals distinct mechanisms underlying BET inhibitor JQ1-mediated modulation of the LPS-induced activation of BV-2 microglial cells. J Neuroinflammation. 2015;12:36.
27. da Huang W, Sherman BT, Lempicki RA. Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc. 2009;4(1):44-57.
28. Kramer A, Green J, Pollard Jr J, Tugendreich S. Causal analysis approaches in Ingenuity Pathway Analysis. Bioinformatics. 2014;30(4):523-30.
29. Zambelli F, Pesole G, Pavesi G. Pscan: finding over-represented transcription factor binding site motifs in sequences from co-regulated or co-expressed genes. Nucleic Acids Res. 2009;37(Web Server issue):W247-252.
30. Portales-Casamar E, Thongjuea S, Kwon AT, Arenillas D, Zhao X, Valen E, Yusuf D, Lenhard B, Wasserman WW, Sandelin A. JASPAR 2010: the greatly expanded open-access database of transcription factor binding profiles. Nucleic Acids Res. 2010;38(Database issue):D105-110.
31. Das A, Chai JC, Kim SH, Lee YS, Park KS, Jung KH, Chai YG. Transcriptome sequencing of microglial cells stimulated with TLR3 and TLR4 ligands. BMC Genomics. 2015;16:517.
32. Dijkstra IM, de Haas AH, Brouwer N, Boddeke HW, Biber K. Challenge with innate and protein antigens induces CCR7 expression by microglia in vitro and in vivo. Glia. 2006;54(8):861-72.
33. Borden EC, Sen GC, Uze G, Silverman RH, Ransohoff RM, Foster GR, Stark GR. Interferons at age 50: past, current and future impact on biomedicine. Nat Rev Drug Discov. 2007;6(12):975-90.
34. Shoemaker ML, Smirnova NP, Bielefeldt-Ohmann H, Austin KJ, van Olphen A, Clapper JA, Hansen TR. Differential expression of the type I interferon pathway during persistent and transient bovine viral diarrhea virus infection. Journal of interferon & cytokine research: the official journal of the International Society for Interferon and Cytokine Research. 2009;29(1):23-35.
35. De Jesus AF, Chen G, Li Z, Grayfer L, Robert J. Susceptibility of Xenopus laevis tadpoles to infection by the ranavirus Frog-Virus 3 correlates with a reduced and delayed innate immune response in comparison with adult frogs. Virology. 2012;432(2):435-43.
36. O'Shea JJ, Plenge R. JAK and STAT signaling molecules in immunoregulation and immune-mediated disease. Immunity. 2012;36(4):542-50.
37. Forero A, Giacobbi NS, McCormick KD, Gjoerup OV, Bakkenist CJ, Pipas JM, Sarkar SN. Simian virus 40 large T antigen induces IFN-stimulated genes through ATR kinase. J Immunol. 2014;192(12):5933-42.
38. Andreoli F, Barbosa AJ, Parenti MD, Del Rio A. Modulation of epigenetic targets for anticancer therapy: clinicopathological relevance, structural data and drug discovery perspectives. Curr Pharm Des. 2013;19(4):578-613.
39. Schliehe C, Flynn EK, Vilagos B, Richson U, Swaminathan S, Bosnjak B, Bauer L, Kandasamy RK, Griesshammer IM, Kosack L et al. The methyltransferase Setdb2 mediates virus-induced susceptibility to bacterial superinfection. Nat Immunol. 2015;16(1):67-74.
40. Ponomarev ED, Veremeyko T, Barteneva N, Krichevsky AM, Weiner HL. MicroRNA-124 promotes microglia quiescence and suppresses EAE by deactivating macrophages via the C/EBP-alpha-PU.1 pathway. Nat Med. 2011;17(1):64-70.
41. Cao M, Cortes M, Moore CS, Leong SY, Durosier LD, Burns P, Fecteau G, Desrochers A, Auer RN, Barreiro LB et al. Fetal microglial phenotype in vitro carries memory of prior in vivo exposure to inflammation. Front Cell Neurosci. 2015;9:294.
42. Takeshita Y, Ransohoff RM. Inflammatory cell trafficking across the blood-brain barrier: chemokine regulation and in vitro models. Immunol Rev. 2012;248(1):228-39.
43. Constantinescu CS, Goodman DB, Hilliard B, Wysocka M, Cohen JA. Murine macrophages stimulated with central and peripheral nervous system myelin or purified myelin proteins release inflammatory products. Neurosci Lett. 2000;287(3):171-4.
44. Zhang Z, Li LY. TNFSF15 modulates neovascularization and inflammation. Cancer microenvironment: official journal of the International Cancer Microenvironment Society. 2012;5(3):237-47.
45. Proudfoot AE, de Souza AL, Muzio V. The use of chemokine antagonists in EAE models. J Neuroimmunol. 2008;198(1-2):27-30.
46. Si Q, Kim MO, Zhao ML, Landau NR, Goldstein H, Lee S. Vpr- and Nef-dependent induction of RANTES/CCL5 in microglial cells. Virology. 2002;301(2):342-53.
47. Lundberg AM, Drexler SK, Monaco C, Williams LM, Sacre SM, Feldmann M, Foxwell BM. Key differences in TLR3/poly I:C signaling and cytokine induction by human primary cells: a phenomenon absent from murine cell systems. Blood. 2007;110(9):3245-52.
48. Williams R, Dhillon NK, Hegde ST, Yao H, Peng F, Callen S, Chebloune Y, Davis RL, Buch SJ. Proinflammatory cytokines and HIV-1 synergistically enhance CXCL10 expression in human astrocytes. Glia. 2009;57(7):734-43.
49. Shen Q, Zhang R, Bhat NR. MAP kinase regulation of IP10/CXCL10 chemokine gene expression in microglial cells. Brain Res. 2006;1086(1):9-16.
50. Lazear HM, Lancaster A, Wilkins C, Suthar MS, Huang A, Vick SC, Clepper L, Thackray L, Brassil MM, Virgin HW et al. IRF-3, IRF-5, and IRF-7 coordinately regulate the type I IFN response in myeloid dendritic cells downstream of MAVS signaling. PLoS Pathog. 2013;9(1):e1003118.
51. Honda K, Yanai H, Negishi H, Asagiri M, Sato M, Mizutani T, Shimada N, Ohba Y, Takaoka A, Yoshida N et al. IRF-7 is the master regulator of type-I interferon-dependent immune responses. Nature. 2005;434(7034):772-7.
52. Inoue M, Williams KL, Gunn MD, Shinohara ML. NLRP3 inflammasome induces chemotactic immune cell migration to the CNS in experimental autoimmune encephalomyelitis. Proc Natl Acad Sci U S A. 2012;109(26):10480-5.
53. Martinon F, Tschopp J. Inflammatory caspases and inflammasomes: master switches of inflammation. Cell Death Differ. 2007;14(1):10-22.
54. Xiao Y, Jin J, Chang M, Chang JH, Hu H, Zhou X, Brittain GC, Stansberg C, Torkildsen O, Wang X. Peli1 promotes microglia-mediated CNS inflammation by regulating Traf3 degradation. Nat Med. 2013;19(5):595-602.
55. Smith AM, Gibbons HM, Oldfield RL, Bergin PM, Mee EW, Curtis MA, Faull RL, Dragunow M. M-CSF increases proliferation and phagocytosis while modulating receptor and transcription factor expression in adult human microglia. J Neuroinflammation. 2013;10:85.
56. Melief J, Koning N, Schuurman KG, Van De Garde MD, Smolders J, Hoek RM, Van Eijk M, Hamann J, Huitinga I. Phenotyping primary human microglia: tight regulation of LPS responsiveness. Glia. 2012;60(10):1506-17.
57. Lai AY, Dibal CD, Armitage GA, Winship IR, Todd KG. Distinct activation profiles in microglia of different ages: a systematic study in isolated embryonic to aged microglial cultures. Neuroscience. 2013;254:185-95.
58. Njie EG, Boelen E, Stassen FR, Steinbusch HW, Borchelt DR, Streit WJ. Ex vivo cultures of microglia from young and aged rodent brain reveal age-related changes in microglial function. Neurobiol Aging. 2012;33(1):195 e191-112.
59. Hanisch UK. Functional diversity of microglia-how heterogeneous are they to begin with? Front Cell Neurosci. 2013;7:65.
60. Hanisch UK, Kettenmann H. Microglia: active sensor and versatile effector cells in the normal and pathologic brain. Nat Neurosci. 2007;10(11):1387-94.
61. Tang Y, Le W. Differential roles of M1 and M2 microglia in neurodegenerative diseases. Mol Neurobiol. 2016;53(2):1181-94.
62. Kitamura Y, Taniguchi T, Kimura H, Nomura Y, Gebicke-Haerter PJ. Interleukin-4-inhibited mRNA expression in mixed rat glial and in isolated microglial cultures. J Neuroimmunol. 2000;106(1-2):95-104.
63. Ledeboer A, Breve JJ, Poole S, Tilders FJ, Van Dam AM. Interleukin-10, interleukin-4, and transforming growth factor-beta differentially regulate lipopolysaccharide-induced production of pro-inflammatory cytokines and nitric oxide in co-cultures of rat astroglial and microglial cells. Glia. 2000;30(2):134-42.
64. Siddiqui TA, Lively S, Schlichter LC. Complex molecular and functional outcomes of single versus sequential cytokine stimulation of rat microglia. J Neuroinflammation. 2016;13(1):66.
65. Dohi K, Ohtaki H, Nakamachi T, Yofu S, Satoh K, Miyamoto K, Song D, Tsunawaki S, Shioda S, Aruga T. Gp91phox (NOX2) in classically activated microglia exacerbates traumatic brain injury. J Neuroinflammation. 2010;7:41.
66. Ghosh M, Xu Y, Pearse DD. Cyclic AMP is a key regulator of M1 to M2a phenotypic conversion of microglia in the presence of Th2 cytokines. J Neuroinflammation. 2016;13:9.
67. Gandy S, Heppner FL. Microglia as dynamic and essential components of the amyloid hypothesis. Neuron. 2013;78(4):575-7.
68. Perry VH, Holmes C. Microglial priming in neurodegenerative disease. Nat Rev Neurol. 2014;10(4):217-24.
69. Shimizu E, Kawahara K, Kajizono M, Sawada M, Nakayama H. IL-4-induced selective clearance of oligomeric beta-amyloid peptide(1-42) by rat primary type 2 microglia. J Immunol. 2008;181(9):6503-13.