Abstract

Gamma interferon (IFNgamma) is an essential cytokine for mediation of functions that are obligatory for good health, particularly that mediated through or maintained through CD4 T helper1 (Th1) cells. Further, IFNgamma possesses direct antiviral and anticellular (antitumor) activity. Thus, the development of IFNgamma mimetics has important implications for immune therapy in infectious diseases and cancer.
The Specific Aims listed below directly test both the rational development of such mimetics as well as their use in the mediation of IFNgamma activity. 1. Synthesis of IFNgamma peptide mimetics based on sequence and structural similarity to biologically active IFNgamma C-terminal peptides. 2. Compare several methods for delivery of IFNgamma peptides intracellularly, including chemical modification and use of molecular expression systems. 3. Determine signaling function of IFNgamma peptide mimetics in terms of JAK/STAT activation, upregulation of tumor suppressor gene p21WAF/CIP, and down regulation of neu/HER-2protooncogene in cancer cells. 4. Determine cellular function of IFN? peptide mimetics in terms of antiviral activity, anticellular (antitumor) activity, and upregulation of MHC class II molecules. 5. Determine biological activity of IFNgamma mimetic peptides in mouse models of virus infection and cancer.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI056152-02
Application #
6798822
Study Section
Experimental Immunology Study Section (EI)
Program Officer
Rathbun, Gary
Project Start
2003-09-15
Project End
2007-02-28
Budget Start
2004-03-01
Budget End
2005-02-28
Support Year
2
Fiscal Year
2004
Total Cost
$327,000
Indirect Cost

  Institution

Name
University of Florida
Department
Microbiology/Immun/Virology
Type
Schools of Earth Sciences/Natur
DUNS #
969663814
City
Gainesville
State
FL
Country
United States
Zip Code
32611

  Publications

Johnson, Howard M; Larkin 3rd, Joseph (2017) Editorial: The Dynamic Role of Suppressor of Cytokine Signaling Proteins in the Regulation of Immune and Autoimmune Responses. Front Immunol 8:825
Ahmed, Chulbul M; Dabelic, Rea; Bedoya, Simone Kennedy et al. (2015) A SOCS1/3 Antagonist Peptide Protects Mice Against Lethal Infection with Influenza A Virus. Front Immunol 6:574
Ahmed, Chulbul M; Johnson, Howard M (2014) Short peptide type I interferon mimetics: therapeutics for experimental allergic encephalomyelitis, melanoma, and viral infections. J Interferon Cytokine Res 34:802-9
Larkin 3rd, Joseph; Ahmed, Chulbul M; Wilson, Tenisha D et al. (2013) Regulation of interferon gamma signaling by suppressors of cytokine signaling and regulatory T cells. Front Immunol 4:469
Ahmed, Chulbul M; Noon-Song, Ezra N; Kemppainen, Kaisa et al. (2013) Type I IFN receptor controls activated TYK2 in the nucleus: implications for EAE therapy. J Neuroimmunol 254:101-9
Bedoya, Simone K; Wilson, Tenisha D; Collins, Erin L et al. (2013) Isolation and th17 differentiation of naïve CD4 T lymphocytes. J Vis Exp :e50765
Johnson, Howard M; Noon-Song, Ezra N; Kemppainen, Kaisa et al. (2012) Steroid-like signalling by interferons: making sense of specific gene activation by cytokines. Biochem J 443:329-38
Jager, Lindsey D; Dabelic, Rea; Waiboci, Lilian W et al. (2011) The kinase inhibitory region of SOCS-1 is sufficient to inhibit T-helper 17 and other immune functions in experimental allergic encephalomyelitis. J Neuroimmunol 232:108-18
Collins, Erin L; Jager, Lindsey D; Dabelic, Rea et al. (2011) Inhibition of SOCS1-/- lethal autoinflammatory disease correlated to enhanced peripheral Foxp3+ regulatory T cell homeostasis. J Immunol 187:2666-76
Noon-Song, Ezra N; Ahmed, Chulbul M; Dabelic, Rea et al. (2011) Controlling nuclear JAKs and STATs for specific gene activation by IFN?. Biochem Biophys Res Commun 410:648-53

Showing the most recent 10 out of 18 publications