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Future Research

Conclusion. Selected References. Discussion. Future Research. CD154A, IFN-γ, and IL-10 genes all showed significant stimulation in most of the tested conditions; however, the IL1F9 gene only showed a response to PWM and PHA.

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Future Research

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  1. Conclusion Selected References Discussion Future Research • CD154A, IFN-γ, and IL-10 genes all showed significant stimulation in most of the tested conditions; however, the IL1F9 gene only showed a response to PWM and PHA. • There are 10 cycle difference for PWM and the 5 cycle difference for PHA represent roughly a 1000x fold increase and a 32x fold increase for these two mitogens. • IL1F9 gene, which shows significantly elevated expression in papilloma tissue from patients with severe RRP, is mainly produced by the monocytes in PBMC. Immune cells in the periphery are capable of producing IL-1F9 The cellular sub-type that is primarily producing this cytokine was identified through magnetic separation of monocytes from the PBMC This result has implications for both the innate and adaptive immune response, not only in patients with RRP, but for immunology in general Armstrong, L. R., C. S. Derkay and W. C. Reeves. “ Initial Results from the National Registry for Juvenile-onset Recurrent Respiratory Papillomatosis. RRP Task Force. Arch Otolaryngol Head Neck Surg. Jul 1999: 125(7):743-8  Berglof, E., Ralph Andre, Blair R. Renshaw, Stuart M. Allan, Catherine B. Lawrence, Nancy J. Rothwell and Emmanuel Pinteaux. “IL-1Rrp2 Expression and IL-1F9 (IL-1H1) Actions in Brain Cells” J Neuroimmunol (2003): 139:36  Bishai D, H. Kashima and K. Shah. “The Cost of Juvenile-onset Recurrent Respiratory Papillomatosis.” Arch Otolaryngol Head Neck Surg. Aug 2000; 126(8);935-9.  Bonagura, Vincent R., Frederick P. Siegal, Allan L. Abramson, Frances Santiago-schwarz, Mary Ellen o'reily, Kokila Shah, Domenica Drake, and Bettie M. Steinberg. "Enriched HLA-DQ3 Phenotype and Decreased Class I Major Histocompatibility Complex Antigen Expression in Recurrent Respiratory Papillomatosis." Clinical and Diagnostic Laboratory Immunology (1994): 357-60. Bonagura V. R, L. Hatam, J. DeVoti, F. Zeng and BM Steinberg. “Recurrent respiratory papillomatosis: altered CD8(+) T-cell subsets and T(H)1/T(H)2 cytokine imbalance.” ClinicalImmunology. (1999): 93:302  Bonagura, Vincent R., Andrea Vambutas, James A. DeVoti, David W. Rosenthal, Bettie M. Steinberg, Allan L. Abramson, Mark J. Shikowitz, David W. Gjertson and Elaine F. Reed. “HLA alleles, IFN-γ responses to HPV-11 E6, and disease severity in patients with recurrent respiratory papillomatosis.” Human Immunology. (2004): 65:773-782. Carson, L. F., L. B. Twiggs, M. Fukushima, R. S. Ostrow, A. J. Faras, and T. Okagaki. "Human Genital Papilloma Infections: An Evaluation of Immunologic Competence in the Genital Neoplasia-papilloma Syndrome." Am J Obstet Gynecol 155 (1986): 784-89. Chomarat, Pascale, Jacques Banchereau, Jean Davoust and A. Karolina Palucka. “IL-6 switches the differentiation of monocytes from dendritic cells to macrophages.” Nature Immunology  1, (2000): 510 – 514 DeVoti, James A., B. M. Steinberg, D. W. Rosenthal, L. Hatam, A. Vambutas, A. L. Abramson, M. J. Shikowitz and V. R. Bonagura. “Failure of Gamma Interferon but Not Interleukin-10 Expression in Response to Human Papillomavirus Type 11 E6 Protein in Respiratory Papillomatosis. Clinical Immunology. (2004): 93:302. DeVoti, James A., David W. Roesnthal, Rong Wu, Allan L. Abramson, Bettie M. Steinberg, and Vincent R. Bonagura. "Immune Dysregulation and Tumor-Associated Gene Changes in Recurrent Respiratory Papillomatosis: A Paired Microarray Analysis." Molecular Medicine. (2008): 1-32.  Eicher, Susan A. "Recurrent Respiratory Papillomatosis." Baylor College Of Medicine. 16 Nov. 1991. Bobby R. Alford Department of Otolaryngology-Head and Neck Surgery. 3 Aug. 2008 <http://www.bcm.edu>.  Elkord, Eyad, Paul E. Williams, Howard Kynaston, and Anthony W. Rowbottom. "Human Monocyte Isolation Methods Influence Cytokine Production from in vitro Generated Dendritic Cells."Blackwell Publishing Ltd, Immunology 114 (2004): 204-12.  Fakruddin, J. M., Richard A. Lempicki, Robert J. Gorelick, Jun Yang, Joseph W. Adelsberger, Alfonso J. Garcia-Pineres, Ligia A. Pinto, H. C. Lane, and Tomozumi Imamichi. "Non-infectious Papilloma Virus-ike Particles Inhibit HIV-1 Replication: Implications for Immune Control of HIV-1 Infection by IL-27." Blood (2006): 1-22.  Galluzzi, Luca, Antonella Penna, Elena Bertozzini, Magda Vila, Esther Garces, and Mauro Magnani. "Development of a Real-Time PCR Assay for Rapid Detection and Quantification of Alexandrium minutum (a Dinoflaellate)." Applied and Environmental Microbiology 70 (2004): 1199-206.  García-Pineres AJ, Hildesheim A, Trivett M, et al. Role of DC-SIGN in the activation of dendritic cells by HPV-16 L1 Virus-Like Particle vaccine. Eur J Immunol. 2006;36:437-445  Sandra Olsson, Roger Sundler. “The macrophage beta−glucan receptor mediates arachidonate release induced by zymosan: Essential role for the Src family kinases.” Mol. Immunol. 2007; 44:1509−1515  Sallusto, F and A Lanzavecchia. “The instructive role of dendritic cells on T-cell responses.” Arthritis Res. 2002;4 Suppl 3:S127-32. 2002 May 9.  Shikowitz, Mark J., Allan L. Abramson, Bettie M. Steinberg, James A. DeVoti, Vincent R. Bonagura, Virginia Mullooly, May Nouri, Avigador M. Ronn, Andrew Inglis, John Mcclay, and Katherine Freeman. "Clinical Trial of Photodynamic Therapy with Meso-Tetra (Hydroxyphenyl) Chlorin for Respiratory Papillomatosis." Arch Otolaryngol Head Neck Surg 131 (2005): 99-105. Szeps, Michael, Liselotte Dahlgren, Leena-Maija Aaltonen, John O¨ hd, Lena Kanter-Lewenshon, Hanna Dahlstrand, Eva Munck-Wikland, Dan Grande and Tina Dalianis. “Human Papillomavirus, Viral Load and Prolieferation Rate in Recurrent Respiratory Papilomatosis in Response to Alpha Interferon Treatment.” Journal of General Virology. (2005), 86, 1695–1702 Termini, Lara, Enrique Boccardo, Gustavo H. Esteves, Roberto Hirata, Waleska K. Martins, Anna Estela L. Colo, E Jordao Neves, Luisa L. Villa, and Luiz Reis. "Chracterization of Global Transcription Profile of Normal and HPV-immortalized Keratinocytes and their Response to TNF Treatment." BMC Medical Genomics. 1 (2008): 29. Towne, J. E., K. E. Garka, B. R. Renshaw, G. D. Virca, and J. E. Sims. “Interleukin (IL)-1F6, IL-1F8, and IL-1F9 Signal through IL-1Rrp2 and IL-1RAcP to Activate the Pathway Leading to NF-_B and MAPKs” J Biol Chem (2004):279:13677- 13688  Yang R, Murillo FM, Cui H, et al. “Papillomavirus-like Particles Stimulate Murine Bone Marrow-derived Dendritic Cells to Produce Alpha Interferon and Th1 Immune Responses via MyD88.” J Virol. 2004;78:11152-11160. Further studies will focus on the primary role and function of IL1F9 on innate and adaptive immune response. Future studies will involve papilloma tissue or patient sample to directly examine the new findings from this study in actual patients.

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