期刊论文详细信息
Journal of Neuroinflammation
Molecular profile of cochlear immunity in the resident cells of the organ of Corti
Bo Hua Hu2  Youyi Dong2  Daniel Cartwright2  Jennifer Jamison3  Jonathan Bard3  Shuzhi Yang1  R Robert Vethanayagam2  Qunfeng Cai2 
[1] Department of Otolaryngology, The first affiliated Hospital to Chinese PLA General Hospital, 51, Fucheng Road, Haidian District, Beijing 100048, China;Center for Hearing and Deafness, State University of New York at Buffalo, 137 Cary Hall, 3435 Main Street, Buffalo 14214, NY, USA;Next-Generation Sequencing and Expression Analysis Core, New York State Center of Excellence in Bioinformatics and Life Sciences, State University of New York at Buffalo, 701 Ellicott Street, Buffalo 14260, NY, USA
关键词: Supporting cells;    Inflammation;    Sensory cells;    Noise;    The organ of Corti;    Immunity;   
Others  :  1150490
DOI  :  10.1186/s12974-014-0173-8
 received in 2014-07-09, accepted in 2014-09-25,  发布年份 2014
PDF
【 摘 要 】

Background

The cochlea is the sensory organ of hearing. In the cochlea, the organ of Corti houses sensory cells that are susceptible to pathological insults. While the organ of Corti lacks immune cells, it does have the capacity for immune activity. We hypothesized that resident cells in the organ of Corti were responsible for the stress-induced immune response of the organ of Corti. This study profiled the molecular composition of the immune system in the organ of Corti and examined the immune response of non-immune epithelial cells to acoustic overstimulation.

Methods

Using high-throughput RNA-sequencing and qRT-PCR arrays, we identified immune- and inflammation-related genes in both the cochlear sensory epithelium and the organ of Corti. Using bioinformatics analyses, we cataloged the immune genes expressed. We then examined the response of these genes to acoustic overstimulation and determined how changes in immune gene expression were related to sensory cell damage.

Results

The RNA-sequencing analysis reveals robust expression of immune-related genes in the cochlear sensory epithelium. The qRT-PCR array analysis confirms that many of these genes are constitutively expressed in the resident cells of the organ of Corti. Bioinformatics analyses reveal that the genes expressed are linked to the Toll-like receptor signaling pathway. We demonstrate that expression of Toll-like receptor signaling genes is predominantly from the supporting cells in the organ of Corti cells. Importantly, our data demonstrate that these Toll-like receptor pathway genes are able to respond to acoustic trauma and that their expression changes are associated with sensory cell damage.

Conclusion

The cochlear resident cells in the organ of Corti have immune capacity and participate in the cochlear immune response to acoustic overstimulation.

【 授权许可】

   
2014 Cai et al.; licensee BioMed Central Ltd.

【 预 览 】
附件列表
Files Size Format View
20150405190703377.pdf 4388KB PDF download
Figure 10. 100KB Image download
Figure 9. 178KB Image download
Figure 8. 39KB Image download
Figure 7. 38KB Image download
Figure 6. 28KB Image download
Figure 5. 49KB Image download
Figure 4. 85KB Image download
Figure 3. 147KB Image download
Figure 2. 103KB Image download
Figure 1. 40KB Image download
【 图 表 】

Figure 1.

Figure 2.

Figure 3.

Figure 4.

Figure 5.

Figure 6.

Figure 7.

Figure 8.

Figure 9.

Figure 10.

【 参考文献 】
  • [1]Hu BH, Henderson D, Nicotera TM: Involvement of apoptosis in progression of cochlear lesion following exposure to intense noise. Hear Res 2002, 166:62-71.
  • [2]Nakashima T, Teranishi M, Hibi T, Kobayashi M, Umemura M: Vestibular and cochlear toxicity of aminoglycosides - a review. Acta Otolaryngol 2000, 120:904-911.
  • [3]Keithley EM, Feldman ML: Hair cell counts in an age-graded series of rat cochleas. Hear Res 1982, 8:249-262.
  • [4]Iwai H, Lee S, Inaba M, Sugiura K, Baba S, Tomoda K, Yamashita T, Ikehara S: Correlation between accelerated presbycusis and decreased immune functions. Exp Gerontol 2003, 38:319-325.
  • [5]Iwai H, Baba S, Omae M, Lee S, Yamashita T, Ikehara S: Maintenance of systemic immune functions prevents accelerated presbycusis. Brain Res 2008, 1208:8-16.
  • [6]Oh GS, Kim HJ, Choi JH, Shen A, Kim CH, Kim SJ, Shin SR, Hong SH, Kim Y, Park C, Lee SJ, Akira S, Park R, So HS: Activation of lipopolysaccharide-TLR4 signaling accelerates the ototoxic potential of cisplatin in mice. J Immunol 2011, 186:1140-1150.
  • [7]Tan WJ, Thorne PR, Vlajkovic SM: Noise-induced cochlear inflammation. World J Otorhinolaryngol 2013, 3:89-99.
  • [8]Fredelius L: Time sequence of degeneration pattern of the organ of Corti after acoustic overstimulation. A transmission electron microscopy study. Acta Otolaryngol 1988, 106:373-385.
  • [9]Tornabene SV, Sato K, Pham L, Billings P, Keithley EM: Immune cell recruitment following acoustic trauma. Hear Res 2006, 222:115-124.
  • [10]Wakabayashi K, Fujioka M, Kanzaki S, Okano HJ, Shibata S, Yamashita D, Masuda M, Mihara M, Ohsugi Y, Ogawa K, Okano H: Blockade of interleukin-6 signaling suppressed cochlear inflammatory response and improved hearing impairment in noise-damaged mice cochlea. Neurosci Res 2010, 66:345-352.
  • [11]Fujioka M, Kanzaki S, Okano HJ, Masuda M, Ogawa K, Okano H: Proinflammatory cytokines expression in noise-induced damaged cochlea. J Neurosci Res 2006, 83:575-583.
  • [12]Hirose K, Discolo CM, Keasler JR, Ransohoff R: Mononuclear phagocytes migrate into the murine cochlea after acoustic trauma. J Comp Neurol 2005, 489:180-194.
  • [13]Miyao M, Firestein GS, Keithley EM: Acoustic trauma augments the cochlear immune response to antigen. Laryngoscope 2008, 118:1801-1808.
  • [14]Du X, Choi CH, Chen K, Cheng W, Floyd RA, Kopke RD: Reduced formation of oxidative stress biomarkers and migration of mononuclear phagocytes in the cochleae of chinchilla after antioxidant treatment in acute acoustic trauma. Int J Otolaryngol 2011, 2011:612690.
  • [15]Sautter NB, Shick EH, Ransohoff RM, Charo IF, Hirose K: CC chemokine receptor 2 is protective against noise-induced hair cell death: studies in CX3CR1(+/GFP) mice. J Assoc Res Otolaryngol 2006, 7:361-372.
  • [16]Okano T, Nakagawa T, Kita T, Kada S, Yoshimoto M, Nakahata T, Ito J: Bone marrow-derived cells expressing Iba1 are constitutively present as resident tissue macrophages in the mouse cochlea. J Neurosci Res 2008, 86:1758-1767.
  • [17]Horner KC, Aurousseau C: Immunoreactivity for taurine in the cochlea: its abundance in supporting cells. Hear Res 1997, 109:135-142.
  • [18]Hashimoto S, Billings P, Harris JP, Firestein GS, Keithley EM: Innate immunity contributes to cochlear adaptive immune responses. Audiol Neurootol 2005, 10:35-43.
  • [19]Hayashi Y, Onomoto K, Narita R, Yoneyama M, Kato H, Nakagawa T, Ito J, Taura A, Fujita T: Virus-induced expression of retinoic acid inducible gene-I and melanoma differentiation-associated gene 5 in the cochlear sensory epithelium. Microbes Infect 2013, 15:592-598.
  • [20]Ladrech S, Mathieu M, Puel JL, Lenoir M: Supporting cells regulate the remodelling of aminoglycoside-injured organ of Corti, through the release of high mobility group box 1. Eur J Neurosci 2013, 38:2962-2972.
  • [21]Cai Q, Wang B, Patel M, Yang SM, Hu BH: RNAlater facilitates microdissection of sensory cell-enriched samples from the mouse cochlea for transcriptional analyses. J Neurosci Methods 2013, 219:240-251.
  • [22]Johnson KR, Erway LC, Cook SA, Willott JF, Zheng QY: A major gene affecting age-related hearing loss in C57BL/6 J mice. Hear Res 1997, 114:83-92.
  • [23]Willott JF: Effects of aging, hearing loss, and anatomical location on thresholds of inferior colliculus neurons in C57BL/6 and CBA mice. J Neurophysiol 1986, 56:391-408.
  • [24]Hunter KP, Willott JF: Aging and the auditory brainstem response in mice with severe or minimal presbycusis. Hear Res 1987, 30:207-218.
  • [25]Hu BH, Cai Q, Hu Z, Patel M, Bard J, Jamison J, Coling D: Metalloproteinases and their associated genes contribute to the functional integrity and noise-induced damage in the cochlear sensory epithelium. J Neurosci 2012, 32:14927-14941.
  • [26]Trapnell C, Pachter L, Salzberg SL: TopHat: discovering splice junctions with RNA-Seq. Bioinformatics 2009, 25:1105-1111.
  • [27]Langmead B, Trapnell C, Pop M, Salzberg SL: Ultrafast and memory-efficient alignment of short DNA sequences to the human genome. Genome Biol 2009, 10:R25. BioMed Central Full Text
  • [28]Trapnell C, Williams BA, Pertea G, Mortazavi A, Kwan G, van Baren MJ, Salzberg SL, Wold BJ, Pachter L: Transcript assembly and quantification by RNA-Seq reveals unannotated transcripts and isoform switching during cell differentiation. Nat Biotechnol 2010, 28:511-515.
  • [29]Mortazavi A, Williams BA, McCue K, Schaeffer L, Wold B: Mapping and quantifying mammalian transcriptomes by RNA-Seq. Nat Methods 2008, 5:621-628.
  • [30]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, 25:402-408.
  • [31]Hu BH, Cai Q: Acoustic overstimulation modifies Mcl-1 expression in cochlear sensory epithelial cells. J Neurosci Res 2010, 88:1812-1821.
  • [32]Cai Q, Patel M, Coling D, Hu BH: Transcriptional changes in adhesion-related genes are site-specific during noise-induced cochlear pathogenesis. Neurobiol Dis 2012, 45:723-732.
  • [33]da Huang W, Sherman BT, Lempicki RA: Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc 2009, 4:44-57.
  • [34]Costa V, Angelini C, D'Apice L, Mutarelli M, Casamassimi A, Sommese L, Gallo MA, Aprile M, Esposito R, Leone L, Aprile M, Esposito R, Leone L, Donizetti A, Crispi S, Rienzo M, Sarubbi B, Calabro R, Picardi M, Salvatore P, Infante T, De Berardinis P, Napoli C, Ciccodicola A: Massive-scale RNA-Seq analysis of non ribosomal transcriptome in human trisomy 21. PLoS One 2011, 6:e18493.
  • [35]Lundberg E, Fagerberg L, Klevebring D, Matic I, Geiger T, Cox J, Algenas C, Lundeberg J, Mann M, Uhlen M: Defining the transcriptome and proteome in three functionally different human cell lines. Mol Syst Biol 2010, 6:450.
  • [36]Flock A, Bretscher A, Weber K: Immunohistochemical localization of several cytoskeletal proteins in inner ear sensory and supporting cells. Hear Res 1982, 7:75-89.
  • [37]Pack AK, Slepecky NB: Cytoskeletal and calcium-binding proteins in the mammalian organ of Corti: cell type-specific proteins displaying longitudinal and radial gradients. Hear Res 1995, 91:119-135.
  • [38]Slepecky NB, Henderson CG, Saha S: Post-translational modifications of tubulin suggest that dynamic microtubules are present in sensory cells and stable microtubules are present in supporting cells of the mammalian cochlea. Hear Res 1995, 91:136-147.
  • [39]Hallworth R, Luduena RF: Differential expression of beta tubulin isotypes in the adult gerbil cochlea. Hear Res 2000, 148:161-172.
  • [40]Jensen-Smith HC, Eley J, Steyger PS, Luduena RF, Hallworth R: Cell type-specific reduction of beta tubulin isotypes synthesized in the developing gerbil organ of Corti. J Neurocytol 2003, 32:185-197.
  • [41]Parsa A, Webster P, Kalinec F: Deiters cells tread a narrow path - the Deiters cells-basilar membrane junction. Hear Res 2012, 290:13-20.
  • [42]Sikorski K, Chmielewski S, Olejnik A, Wesoly JZ, Heemann U, Baumann M, Bluyssen H: STAT1 as a central mediator of IFNgamma and TLR4 signal integration in vascular dysfunction. JAKSTAT 2012, 1:241-249.
  • [43]Boisson-Dupuis S, Kong XF, Okada S, Cypowyj S, Puel A, Abel L, Casanova JL: Inborn errors of human STAT1: allelic heterogeneity governs the diversity of immunological and infectious phenotypes. Curr Opin Immunol 2012, 24:364-378.
  • [44]Prakash A, Smith E, Lee CK, Levy DE: Tissue-specific positive feedback requirements for production of type I interferon following virus infection. J Biol Chem 2005, 280:18651-18657.
  • [45]Marie I, Durbin JE, Levy DE: Differential viral induction of distinct interferon-alpha genes by positive feedback through interferon regulatory factor-7. EMBO J 1998, 17:6660-6669.
  • [46]O'Mahony DS, Pham U, Iyer R, Hawn TR, Liles WC: Differential constitutive and cytokine-modulated expression of human Toll-like receptors in primary neutrophils, monocytes, and macrophages. Int J Med Sci 2008, 5:1-8.
  • [47]Braunstein J, Brutsaert S, Olson R, Schindler C: STATs dimerize in the absence of phosphorylation. J Biol Chem 2003, 278:34133-34140.
  • [48]Poltorak A, He X, Smirnova I, Liu MY, Van Huffel C, Du X, Birdwell D, Alejos E, Silva M, Galanos C, Freudenberg M, Ricciardi-Castagnoli P, Layton B, Beutler B: Defective LPS signaling in C3H/HeJ and C57BL/10ScCr mice: mutations in Tlr4 gene. Science 1998, 282:2085-2088.
  • [49]Zheng J, Shen W, He DZ, Long KB, Madison LD, Dallos P: Prestin is the motor protein of cochlear outer hair cells. Nature 2000, 405:149-155.
  • [50]Pascuan CG, Uran SL, Gonzalez-Murano MR, Wald MR, Guelman LR, Genaro AM: Immune alterations induced by chronic noise exposure: comparison with restraint stress in BALB/c and C57Bl/6 mice. J Immunotoxicol 2014, 11:78-83.
  • [51]Tra Y, Frisina R, D'Souza M: A novel high-throughput analysis approach: immune response-related genes are upregulated in age-related hearing loss. Open Access Bioinformatics 2011, 3:107-122.
  • [52]Fredelius L, Rask-Andersen H: The role of macrophages in the disposal of degeneration products within the organ of Corti after acoustic overstimulation. Acta Otolaryngol 1990, 109:76-82.
  • [53]Satoh H, Firestein GS, Billings PB, Harris JP, Keithley EM: Tumor necrosis factor-alpha, an initiator, and etanercept, an inhibitor of cochlear inflammation. Laryngoscope 2002, 112:1627-1634.
  • [54]Ichimiya I, Yoshida K, Hirano T, Suzuki M, Mogi G: Significance of spiral ligament fibrocytes with cochlear inflammation. Int J Pediatr Otorhinolaryngol 2000, 56:45-51.
  • [55]Nakamoto T, Mikuriya T, Sugahara K, Hirose Y, Hashimoto T, Shimogori H, Takii R, Nakai A, Yamashita H: Geranylgeranylacetone suppresses noise-induced expression of proinflammatory cytokines in the cochlea. Auris Nasus Larynx 2012, 39:270-274.
  • [56]Hertzano R, Puligilla C, Chan SL, Timothy C, Depireux DA, Ahmed Z, Wolf J, Eisenman DJ, Friedman TB, Riazuddin S, Kelley MW, Strome SE: CD44 is a marker for the outer pillar cells in the early postnatal mouse inner ear. J Assoc Res Otolaryngol 2010, 11:407-418.
  • [57]Patel M, Hu Z, Bard J, Jamison J, Cai Q, Hu BH: Transcriptome characterization by RNA-Seq reveals the involvement of the complement components in noise-traumatized rat cochleae. Neuroscience 2013, 248C:1-16.
  • [58]Raphael Y, Altschuler RA: Reorganization of cytoskeletal and junctional proteins during cochlear hair cell degeneration. Cell Motil Cytoskeleton 1991, 18:215-227.
  • [59]Abrashkin KA, Izumikawa M, Miyazawa T, Wang CH, Crumling MA, Swiderski DL, Beyer LA, Gong TW, Raphael Y: The fate of outer hair cells after acoustic or ototoxic insults. Hear Res 2006, 218:20-29.
  • [60]Takahashi K, Koga K, Linge HM, Zhang Y, Lin X, Metz CN, Al-Abed Y, Ojamaa K, Miller EJ: Macrophage CD74 contributes to MIF-induced pulmonary inflammation. Respir Res 2009, 10:33. BioMed Central Full Text
  • [61]Flaster H, Bernhagen J, Calandra T, Bucala R: The macrophage migration inhibitory factor-glucocorticoid dyad: regulation of inflammation and immunity. Mol Endocrinol 2007, 21:1267-1280.
  • [62]Keithley EM, Wang X, Barkdull GC: Tumor necrosis factor alpha can induce recruitment of inflammatory cells to the cochlea. Otol Neurotol 2008, 29:854-859.
  • [63]Akira S, Takeda K: Toll-like receptor signalling. Nat Rev Immunol 2004, 4:499-511.
  • [64]Tang SC, Arumugam TV, Xu X, Cheng A, Mughal MR, Jo DG, Lathia JD, Siler DA, Chigurupati S, Ouyang X, Magnus T, Camandola S, Mattson MP: Pivotal role for neuronal Toll-like receptors in ischemic brain injury and functional deficits. Proc Natl Acad Sci U S A 2007, 104:13798-13803.
  文献评价指标  
  下载次数:38次 浏览次数:7次