1482 Role of IRFs in Virus-Induced IL-23 p19 Promoter in Macrophages

Saturday, March 24, 2012: 9:45 a.m. - 11 a.m.
Presentation Type: Poster Session
R.K. BUNDY, T. PETRO, and T. MOORE, Oral Biology, University of Nebraska, Lincoln, NE
Objectives: Chronic infections of each human with 8-10 viruses sometimes lead to inflammatory or autoimmune diseases.  IL-23 plays a key role in many autoimmune and inflammatory diseases, like periodontitis.  In a model of chronic virus infection leading to disease, SJL/J mice are susceptible to chronic infection with Theiler’s murine encephalomyelitis virus (TMEV) while B10.S mice are not.  Interestingly, macrophages express IL-23 in response to TMEV and the transcription factor IRF-3 plays a role in expression of the IL-23 p19 subunit.  However, other member of the IRF family, such as IRF-1 or IRF-7, may also have a role in p19 expression. The hypothesis here is that IRF-1 and/or IRF-7 are also involved in p19 expression by macrophages challenged with TMEV.

Methods: Primary macrophages from SJL/J (TMEV susceptible), B10.S (TMEV resistant) were challenged with TMEV and IRF1 and IRF7 protein evaluated by western blot. Following challenge with TMEV both sets of macrophages expressed IRF1 and IRF7.  To determine the ability of IRF1 and IRF7 to stimulate p19 promoter activity, the RAW264.7 macrophage cell line was transfected the p19 promoter luciferase-reporter vector with or without IRF1 or IRF7 expression vectors before challenge with TMEV.  Both IRF1 and IRF7 overexpression stimulated p19 promoter activity.  To confirm whether IRF1, IRF3, and IRF7 interact with the p19 promoter, fluorescent-tagged oligos corresponding to two IRF consensus sites (IRFE1 and IRFE2) of the p19 promoter were mixed with nuclear extracts of TMEV-challenged RAW264.7 cells and evaluated by EMSA supershift.

Results: The results confirm that IRF7 but not IRF1 or IRF3 bound to p19IRFE1 while IRF3 and IRF7 but not IRF1 bound to p19IRFE2.


Therefore, IRF1, IRF3, and IRF7 play a significant role in expression of pro-inflammatory IL-23 in macrophages challenged with viruses and thus could have a role in sustaining inflammation as a result of chronic virus infection.

This abstract is based on research that was funded entirely or partially by an outside source: UNIVERSITY OF NEBRASKA MEDICAL CENTER COLLEGE OF DENTISTRY STUDENT SUMMER RESEARCH FELLOWSHIP

Keywords: Gene expression, Immune response, Immunology, Inflammatory mediators and Periodontal disease
See more of: Immunology
See more of: Microbiology / Immunology