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Protein Microarrays: Effective Tools for the Study of Inflammatory Diseases

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Reverse Chemical Genetics

Part of the book series: Methods in Molecular Biology™ ((MIMB,volume 577))

Summary

Inflammation is a defense reaction of an organism against harmful stimuli such as tissue injury or infectious agents. The relationship between the infecting microorganism and the immune, inflammatory, and coagulation responses of the host is intricately intertwined. Due to its complex nature, the molecular mechanisms of inflammation are not yet understood in detail and additional diagnostic tools are required to clarify further aspects. In recent years, protein microarray-based research has moved from being technology-based to application-oriented. Protein microarrays are perfect tools for studying inflammatory diseases. High-density protein arrays enable new classes of autoantibodies, which cause autoimmune diseases, to be discovered. Protein arrays consisting of miniaturized multiplexed sandwich immunoassays allow the simultaneous expression analysis of dozens of signaling molecules such as the cytokines and chemokines involved in the regulation of the immune system. The data enable statements to be made on the status of the disease and its progression as well as support for the clinicians in choosing patient-specific treatment. This chapter reviews the technology and the applications of protein microarrays in diagnosing and monitoring inflammatory diseases.

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References

  1. Lissauer, M.E., et al. (2007) Coagulation and complement protein differences between septic and uninfected systemic inflammatory response syndrome patients. J Trauma. 62, 1082–92; discussion 1092–4.

    Article  PubMed  CAS  Google Scholar 

  2. Tracey, K.J. (2002) The inflammatory reflex. Nature. 420, 853–9.

    Article  PubMed  CAS  Google Scholar 

  3. Carrigan, S.D., G. Scott, and M. Tabrizian (2004) Toward resolving the challenges of sepsis diagnosis. Clin Chem. 50, 1301–14.

    Article  PubMed  CAS  Google Scholar 

  4. Hotchkiss, R.S. and D.W. Nicholson (2006) Apoptosis and caspases regulate death and inflammation in sepsis. Nat Rev Immunol. 6, 813–22.

    Article  PubMed  CAS  Google Scholar 

  5. Kemper, C. and J.P. Atkinson (2007) T-cell regulation: with complements from innate immunity. Nat Rev Immunol. 7, 9–18.

    Article  PubMed  CAS  Google Scholar 

  6. Lin, W.W. and M. Karin (2007) A cytokine-mediated link between innate immunity, inflammation, and cancer. J Clin Invest. 117, 1175–83.

    Article  PubMed  CAS  Google Scholar 

  7. Purwar, R., et al. (2008) Modulation of keratinocyte-derived MMP-9 by IL-13: a possible role for the pathogenesis of epidermal inflammation. J Invest Dermatol. 128, 59–66.

    Article  PubMed  CAS  Google Scholar 

  8. Stoll, D., et al. (2005) Protein microarrays: applications and future challenges. Curr Opin Drug Discov Devel. 8, 239–52.

    PubMed  CAS  Google Scholar 

  9. Kricka, L.J., et al. (2006) Current perspectives in protein array technology. Ann Clin Biochem. 43, 457–67.

    Article  PubMed  CAS  Google Scholar 

  10. Master, S.R., C. Bierl, and L.J. Kricka (2006) Diagnostic challenges for multiplexed protein microarrays. Drug Discov Today. 11, 1007–11.

    Article  PubMed  CAS  Google Scholar 

  11. Chipping-Forecast-II (2002) Nature Genetics, 32(supplement), 461–552.

    Google Scholar 

  12. Stoll, D., et al. (2002) Protein microarray technology. Front Biosci. 7, c13–32.

    Article  PubMed  CAS  Google Scholar 

  13. Liu, Y., et al. (2007) Optimization of printing buffer for protein microarrays based on aldehyde-modified glass slides. Front Biosci. 12, 3768–73.

    Article  PubMed  CAS  Google Scholar 

  14. Oh, S.J., et al. (2006) Surface modification for DNA and protein microarrays. OMICS. 10, 327–43.

    Article  PubMed  CAS  Google Scholar 

  15. Matson, R.S., et al. (2007) Overprint immunoassay using protein A microarrays. Methods Mol Biol. 382, 273–86.

    Article  PubMed  CAS  Google Scholar 

  16. Li, Y.J., et al. (2006) Reversible immobilization of proteins with streptavidin affinity tags on a surface plasmon resonance biosensor chip. Anal Bioanal Chem. 386, 1321–6.

    Article  PubMed  CAS  Google Scholar 

  17. Zhu, H., et al. (2001) Global analysis of protein activities using proteome chips. Science. 293, 2101–5.

    Article  PubMed  CAS  Google Scholar 

  18. Lauer, S.A. and J.P. Nolan (2002) Development and characterization of Ni-NTA-bearing microspheres. Cytometry. 48, 136–45.

    Article  PubMed  CAS  Google Scholar 

  19. Waterboer, T., et al. (2005) Multiplex human papillomavirus serology based on in situ-purified glutathione s-transferase fusion proteins. Clin Chem. 51, 1845–53.

    Article  PubMed  CAS  Google Scholar 

  20. Boozer, C., et al. (2006) DNA-directed protein immobilization for simultaneous detection of multiple analytes by surface plasmon resonance biosensor. Anal Chem. 78, 1515–9.

    Article  PubMed  CAS  Google Scholar 

  21. Lee, M., et al. (2006) Protein nanoarray on Prolinker surface constructed by atomic force microscopy dip-pen nanolithography for analysis of protein interaction. Proteomics. 6, 1094–103.

    Article  PubMed  CAS  Google Scholar 

  22. Wang, Z., T. Wilkop, and Q. Cheng (2005), Characterization of micropatterned lipid membranes on a gold surface by surface plasmon resonance imaging and electrochemical signaling of a pore-forming protein. Langmuir. 21, 10292–6.

    Article  PubMed  CAS  Google Scholar 

  23. Rozkiewicz, D.I., et al. (2007) Dendrimer-mediated transfer printing of DNA and RNA microarrays. J Am Chem Soc. 129, 11593–9.

    Article  PubMed  CAS  Google Scholar 

  24. Mayer, M., et al. (2004) Micropatterned agarose gels for stamping arrays of proteins and gradients of proteins. Proteomics. 4, 2366–76.

    Article  PubMed  CAS  Google Scholar 

  25. Palmer, R.E. and C. Leung (2007) Immobilisation of proteins by atomic clusters on surfaces. Trends Biotechnol. 25, 48–55.

    Article  PubMed  CAS  Google Scholar 

  26. Barbulovic-Nad, I., et al. (2006) Bio-microarray fabrication techniques – a review. Crit Rev Biotechnol. 26, 237–59.

    Article  PubMed  CAS  Google Scholar 

  27. Pawlak, M., et al. (2002) Zeptosens’ protein microarrays: a novel high performance microarray platform for low abundance protein analysis. Proteomics. 2, 383–93.

    Article  PubMed  CAS  Google Scholar 

  28. Usui-Aoki, K., K. Shimada, and H. Koga (2007) A novel antibody microarray format using non-covalent antibody immobilization with chemiluminescent detection. Mol Biosyst. 3, 36–42.

    Article  PubMed  CAS  Google Scholar 

  29. Guo, H., et al. (2005) Development of a low density colorimetric protein array for cardiac troponin I detection. J Nanosci Nanotechnol. 5, 2161–6.

    Article  PubMed  CAS  Google Scholar 

  30. Timlin, J.A. (2006) Scanning microarrays: current methods and future directions. Methods Enzymol. 411, 79–98.

    Article  PubMed  CAS  Google Scholar 

  31. Yu, X., D. Xu, and Q. Cheng (2006) Label-free detection methods for protein microarrays. Proteomics. 6, 5493–503.

    Article  PubMed  CAS  Google Scholar 

  32. Kingsmore, S.F. (2006) Multiplexed protein measurement: technologies and applications of protein and antibody arrays. Nat Rev Drug Discov. 5, 310–20.

    Article  PubMed  CAS  Google Scholar 

  33. Templin, M.F., et al. (2002) Protein microarray technology. Trends Biotechnol. 20, 160–6.

    Article  PubMed  CAS  Google Scholar 

  34. Mendes, K.N., et al. (2007) Analysis of signaling pathways in 90 cancer cell lines by protein lysate array. J Proteome Res. 6, 2753–67.

    Article  PubMed  CAS  Google Scholar 

  35. Sheehan, K.M., et al. (2008) Signal pathway profiling of epithelial and stromal compartments of colonic carcinoma reveals epithelial-mesenchymal transition. Oncogene. 27, 323–31.

    Article  PubMed  CAS  Google Scholar 

  36. Geho, D.H., et al. (2007) Fluorescence-based analysis of cellular protein lysate arrays using quantum dots. Methods Mol Biol. 374, 229–37.

    PubMed  CAS  Google Scholar 

  37. Templin, M.F., et al. (2004) Protein microarrays and multiplexed sandwich immunoassays: what beats the beads? Comb Chem High Throughput Screen. 7, 223–9.

    PubMed  CAS  Google Scholar 

  38. http://www.biochipnet.de, Biochipnet.

  39. Singh, M. and L. Johnson (2006) Using genetically engineered mouse models of cancer to aid drug development: an industry perspective. Clin Cancer Res. 12, 5312–28.

    Article  PubMed  CAS  Google Scholar 

  40. Toy, D., et al. (2006) Cutting edge: interleukin 17 signals through a heteromeric receptor complex. J Immunol. 177, 36–9.

    PubMed  CAS  Google Scholar 

  41. Perper, S.J., et al. (2006) TWEAK is a novel arthritogenic mediator. J Immunol. 177, 2610–20.

    PubMed  CAS  Google Scholar 

  42. Fath, M.A., et al. (2005) Mkks-null mice have a phenotype resembling Bardet–sBiedl syndrome. Hum Mol Genet. 14, 1109–18.

    Article  PubMed  CAS  Google Scholar 

  43. Heuer, J.G., et al. (2004) Evaluation of protein C and other biomarkers as predictors of mortality in a rat cecal ligation and puncture model of sepsis. Crit Care Med. 32, 1570–8.

    Article  PubMed  CAS  Google Scholar 

  44. Heuer, J.G., D.J. Cummins, and B.T. Edmonds (2005) Multiplex proteomic approaches to sepsis research: case studies employing new technologies. Expert Rev Proteomics. 2, 669–80.

    Article  PubMed  CAS  Google Scholar 

  45. Hsu, H.Y., S. Wittemann, and T.O. Joos (2008) Miniaturized parallelized sandwich immunoassays. Methods Mol Biol. 428, 247–61.

    Article  PubMed  CAS  Google Scholar 

  46. Kader, H.A., et al. (2005) Protein microarray analysis of disease activity in pediatric inflammatory bowel disease demonstrates elevated serum PLGF, IL-7, TGF-beta1, and IL-12p40 levels in Crohn’s disease and ulcerative colitis patients in remission versus active disease. Am J Gastroenterol. 100, 414–23.

    Article  PubMed  CAS  Google Scholar 

  47. Decalf, J., et al. (2007) Plasmacytoid dendritic cells initiate a complex chemokine and cytokine network and are a viable drug target in chronic HCV patients. J Exp Med. 204, 2423–37.

    Article  PubMed  CAS  Google Scholar 

  48. Tang, X., et al. (2005) LPS induces the interaction of a transcription factor, LPS-induced TNF-alpha factor, and STAT6(B) with effects on multiple cytokines. Proc Natl Acad Sci U S A. 102, 5132–7.

    Article  PubMed  CAS  Google Scholar 

  49. Datta, A., et al. (2006) The HTLV-I p30 interferes with TLR4 signaling and modulates the release of pro- and anti-inflammatory cytokines from human macrophages. J Biol Chem. 281, 23414–24.

    Article  PubMed  CAS  Google Scholar 

  50. Andreas, K., et al. (2008) Key regulatory molecules of cartilage destruction in rheumatoid arthritis: an in vitro study. Arthritis Res Ther. 10, R9.

    Article  PubMed  Google Scholar 

  51. Hueber, W., et al. (2005) Antigen microarray profiling of autoantibodies in rheumatoid arthritis. Arthritis Rheum. 52, 2645–55.

    Article  PubMed  CAS  Google Scholar 

  52. Hudson, M.E., et al. (2007) Identification of differentially expressed proteins in ovarian cancer using high-density protein microarrays. Proc Natl Acad Sci USA. 104, 17494–9.

    Article  PubMed  CAS  Google Scholar 

  53. Celis, J.E., et al. (2004) Proteomic characterization of the interstitial fluid perfusing the breast tumor microenvironment: a novel resource for biomarker and therapeutic target discovery. Mol Cell Proteomics. 3, 327–44.

    Article  PubMed  CAS  Google Scholar 

  54. Kline, M., et al. (2007) Cytokine and chemokine profiles in multiple myeloma; significance of stromal interaction and correlation of IL-8 production with disease progression. Leuk Res. 31, 591–8.

    Article  PubMed  CAS  Google Scholar 

  55. Carson, R.T. and D.A. Vignali (1999) Simultaneous quantitation of 15 cytokines using a multiplexed flow cytometric assay. J Immunol Methods. 227, 41–52.

    Article  PubMed  CAS  Google Scholar 

  56. Prabhakar, U., E. Eirikis, and H.M. Davis (2002) Simultaneous quantification of proinflammatory cytokines in human plasma using the LabMAP assay. J Immunol Methods. 260, 207–18.

    Article  PubMed  CAS  Google Scholar 

  57. de Jager, W., et al. (2003) Simultaneous detection of 15 human cytokines in a single sample of stimulated peripheral blood mononuclear cells. Clin Diagn Lab Immunol. 10, 133–9.

    PubMed  Google Scholar 

  58. Olsson, A., et al. (2005) Simultaneous measurement of beta-amyloid(1–42), total tau, and phosphorylated tau (Thr181) in cerebrospinal fluid by the xMAP technology. Clin Chem. 51, 336–45.

    Article  PubMed  CAS  Google Scholar 

  59. de Jager, W. and G.T. Rijkers (2006) Solid-phase and bead-based cytokine immunoassay: a comparison. Methods. 38, 294–303.

    Article  PubMed  Google Scholar 

  60. Maier, R., et al. (2006) Application of multiplex cytometric bead array technology for the measurement of angiogenic factors in the vitreous. Mol Vis. 12, 1143–7.

    PubMed  CAS  Google Scholar 

  61. McDuffie, E., et al. (2006) Detection of cytokine protein expression in mouse lung homogenates using suspension bead array. J Inflamm (Lond). 3, 15.

    Article  Google Scholar 

  62. Kofoed, K., et al. (2007) Use of plasma C-reactive protein, procalcitonin, neutrophils, macrophage migration inhibitory factor, soluble urokinase-type plasminogen activator receptor, and soluble triggering receptor expressed on myeloid cells-1 in combination to diagnose infections: a prospective study. Crit Care. 11, R38.

    Article  PubMed  Google Scholar 

  63. Rossi, D. and A. Zlotnik (2000) The biology of chemokines and their receptors. Annu Rev Immunol. 18, 217–42.

    Article  PubMed  CAS  Google Scholar 

  64. Zlotnik, A. and O. Yoshie (2000) Chemokines: a new classification system and their role in immunity. Immunity. 12, 121–7.

    Article  PubMed  CAS  Google Scholar 

  65. Bozza, F.A., et al. (2007) Cytokine profiles as markers of disease severity in sepsis: a multiplex analysis. Crit Care. 11, R49.

    Article  PubMed  Google Scholar 

  66. Calvano, S.E., et al. (1996) Monocyte tumor necrosis factor receptor levels as a predictor of risk in human sepsis. Arch Surg. 131, 434–7.

    Article  PubMed  CAS  Google Scholar 

  67. Pruitt, J.H., et al. (1996) Increased soluble interleukin-1 type II receptor concentrations in postoperative patients and in patients with sepsis syndrome. Blood. 87, 3282–8.

    PubMed  CAS  Google Scholar 

  68. Keh, D., et al. (2003) Immunologic and hemodynamic effects of “low-dose” hydrocortisone in septic shock: a double-blind, randomized, placebo-controlled, crossover study. Am J Respir Crit Care Med. 167, 512–20.

    Article  PubMed  Google Scholar 

  69. Hsu, H.Y., et al. (2008) Suspension microarrays for the identification of the response patterns in hyperinflammatory diseases. Med Eng Phys 30, 976–83.

    Article  PubMed  Google Scholar 

  70. Kofoed, K., et al. (2006) Development and validation of a multiplex add-on assay for sepsis biomarkers using xMAP technology. Clin Chem. 52, 1284–93.

    Article  PubMed  CAS  Google Scholar 

  71. Lin, Y., et al. (2002) Profiling of human cytokines in healthy individuals with vitamin E supplementation by antibody array. Cancer Lett. 187, 17–24.

    Article  PubMed  CAS  Google Scholar 

  72. Zhang, J.Z. and K.W. Ward (2008) Besifloxacin, a novel fluoroquinolone antimicrobial agent, exhibits potent inhibition of pro-inflammatory cytokines in human THP-1 monocytes. J Antimicrob Chemother. 61, 111–6.

    Article  PubMed  CAS  Google Scholar 

  73. Joos, T.O. and H. Berger (2006) The long and difficult road to the diagnostic market: protein microarrays. Drug Discov Today. 11, 959–61.

    Article  PubMed  Google Scholar 

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Acknowledgments

Dr. Xiaobo Yu’s research is supported by a Humboldt research fellowship (Alexander von Humboldt Foundation, Germany; fellowship ID: 1126997). Hsin-Yun Hsu is supported by the DAAD (German Academic Exchange Service), Germany (fellowship ID: A/04/07700).

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Authors and Affiliations

  1. NMI Natural and Medical Sciences Institute at the University of Tübingen, Reutlingen, Germany

    Xiaobo Yu, Nicole Schneiderhan-Marra, Hsin-Yun Hsu & Thomas O. Joos

  2. Bachmann Consulting, Nesoddtangen, Norway

    Jutta Bachmann

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  1. Xiaobo Yu
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  2. Nicole Schneiderhan-Marra
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  3. Hsin-Yun Hsu
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  4. Jutta Bachmann
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  5. Thomas O. Joos
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Editors and Affiliations

  1. Iwai Orthopaedic Medical Hospital, Minamikoiwa 8-17-5, Tokyo, 133-0055, Japan

    Hisashi Koga

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Yu, X., Schneiderhan-Marra, N., Hsu, HY., Bachmann, J., Joos, T.O. (2009). Protein Microarrays: Effective Tools for the Study of Inflammatory Diseases. In: Koga, H. (eds) Reverse Chemical Genetics. Methods in Molecular Biology™, vol 577. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-60761-232-2_15

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  • DOI: https://doi.org/10.1007/978-1-60761-232-2_15

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  • Publisher Name: Humana Press, Totowa, NJ

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