Professor of Microbiology and Immunology
Dept. Oral Biology
University of Nebraska Medical Center
College of Dentistry
40th and Holdrege
Lincoln, NE 68583-0740
The main focus of my laboratory has been the induction of the IL-12 family of cytokines during the innate immune response to viruses. The innate immune response to viral infection is dependent to a large extent upon the induction of Type I interferons (IFN) alpha/beta, IL-12, and IFN-_. Type I interferons create an antiviral state in which protein kinase R, ISG15, ISG54 and IP-10 are produced and the cytotoxic capabilities of NK and NKT cells against virus-infected cells are increased. On the other hand, IL-12 and IFN-gamma increase the proliferation of NK and NKT cells and bring about the expression of inducible nitric oxide synthase (NOS2) and thus nitric oxide, which has potent anti-viral properties. Interestingly, innate anti-viral immunity is internally regulated by Type I interferon control of the IL-12/IFN-gamma/NOS2 nexus and nitric oxide control of Type I interferon expression. Therefore it is possible that one or the other system will dominate an innate anti-viral immune response.
The immune response to viruses is considered necessary for the control of viral replication within the human body. Nevertheless, it has been observed that the tissue destruction brought about by the virus sometimes leads to an autoimmune response against proteins in the body during the adaptive immune response phase of the immune response to the virus. Occasionally, this autoimmune response leads to a chronic autoimmune disease state, such as multiple sclerosis. It is not completely clear what triggers the autoimmune disease during the adaptive phase of the immune response, but production of the IL-12 family of proteins precedes and dominates many of these autoimmune responses. We have found that in an experimental mouse model that the production of this IL-12 family of cytokines is a normal and necessary part of the anti-viral innate immune response. The molecular mechanism by which the IL-12 family of proteins is expressed at the gene level is not known and is the subject of our research. We have and will be examining the role of the IL-12 family of proteins in the induction of nitric oxide (NO), which could cause some of the tissue destruction associated with autoimmune disease but is also part of the normal innate anti-viral immune response.
Selected Recent Publications:
1. Al-Salleeh FM and Petro TM. TLR3 and TLR7 are involved in expression of IL-23 subunits while TLR3 but not TLR7 is involved in expression of IFN-b by Theiler’s virus-infected RAW264.7 cells. Microbes and Infection. 11:1384-92, 2007.
2. Hause L, Al-Salleeh FM and Petro TM. Expression of IL-27 p28 by Theiler’s virus-Infected Macrophages Depends on TLR3 and TLR7 Activation of JNK-MAP-Kinases. Antiviral Research. 76(2) 159-167, 2007.
3. Navarathna DH, Nickerson KW, Duhamel GE, Jerrels TR, Petro TM. Exogenous farnesol interferes with the normal progression of cytokine expression during candidiasis in a mouse model. Infect Immun. 75(8):4006-11, 2007.
4. Kollet, JI and Petro TM. IRF-1 and NF-kB p50/cRel Bind to Distinct Regions of the Proximal Murine IL-12 p35 Promoter During Costimulation with IFN-g and LPS. Molecular Immunology 43: 623-633, 2006.
5. Dahlberg, A, Auble, MR, and Petro TM. Reduced expression of IL-12 p35 by SJL/J macrophages responding to Theiler’s virus infection is associated with constitutive activation of IRF-3. Virology 353: 422-432, 2006.
6. Petro, TM. ERK-MAP-kinases differentially regulate expression of IL-23 p19 compared with p40 and IFN-beta in Theiler's virus-infected RAW264.7 cells. Immunol Lett. 2005 Feb 15;97(1):47-53.
7. Petro, TM. Disparate expression of IL-12 by SJL/J and B10.S macrophages during Theiler's virus infection is associated with activity of TLR7 and Mitogen-activated Protein Kinases, Microbes and Infection 7:224-232, 2005.
8. Vaidyanathan H, Zhou Y, Petro TM, and Schwartzbach SD. Intracellular localization of the p35 subunit of murine IL-12. Cytokine, 21:120-128, 2003
9. Petro TM, Anderson LL, Gowler JS, Liu X, and Schwartzbach SD. Smokeless tobacco extract decreases IL-12 production from LPS-stimulated but decreases IL-12 from IFN-(-stimulated macrophages. International Immunopharmacology. 2:345-355, 2002.
10. Kollet J, Witek C, Gentry JD, Liu X, Schwartzbach SD, and Petro TM. Deletional analysis of the murine IL-12 p35 promoter comparing interferon-( and LPS stimulation. J. Immunol.167:5653-5663, 2001.
1. Petro, TM and Zhang, Y, Theiler's virus induction of p35, p40 and p19 IL-12 family subunits is reduced by a p38 MAP-kinase inhibitor.Presented at the American Association of Immunology Annual Meeting, Denver, CO, May 2003
2. Kollet, J, and Petro, TM. In vivo and in vitro interaction of IRF-1 and c-Rel with the proximal Interleukin p35 promtoer. Presented at the American Association of Immunology Annual Meeting, Denver, CO, May 2003
3. Kollet J, Witek C, Gentry JD, Liu X, Schwartzbach SD, and Petro TM. Recruitment of Interferon Regulatory Factor 1 (IRF-1) to the Interleukin-12 recruitment of Interferon Regulatory Factor 1 (IRF-1) to the Interleukin-12 p35 Promoter upon Interferon-[gamma]/LPS Stimulation35 Promoter upon Interferon-_/LPS Stimulation. 41st American Society for Cell Biology Annual Meeting in Washington, DC, December 8-12, 2001.
4. Petro, T.M., Witek, C., Kollet, J., Liu, X., Schwartzbach, S.D. Distinct regulatory elements in the murine IL-12 p35 promoter respond to Interferon-_ and LPS. Presented at the American Association of Immunology Annual Meeting, Seattle, WA, FASEB J 14(6):A1182:#155, April 14, 2000.
5. Petro, T.M., Gentry, J.D., Weatherman, A., Schwartzbach, S.D. Analysis of murine IL-12 p 35 promoter. Experimental Biology, 1999, Washington, D.C., FASEB J 13(5):A651, March 15, 1999.
1977 - 1980 PhD Immunology/Microbiology, Miami University, Oxford, Ohio
1975 - 1977 MS Microbiology, Miami University, Oxford, Ohio
1972 - 1975 BS Microbiology, Ohio State University, Columbus, Ohio
July 2002 - Present Professor, Department of Oral Biology, University of Nebraska Medical Center, College of Dentistry, Lincoln, Nebraska
1992 - Present Courtesy Appointment, Associate Professor, Dept. of Veterinary & Biomedical Science, University of Nebraska-Lincoln
1991 - 2002 Associate Professor
Department of Oral Biology
University of Nebraska Medical Center
College of Dentistry
1990 - Present Faculty Associate, UNL Center for Biotechnology
1987 - 1991 Assistant Professor, Department of Oral Biology, University of Nebraska Medical Center, College of Dentistry, Lincoln, NE 68583
1984 - 1987 Microbiologist, Microbial Biochemistry Branch, Division of Microbiology, Food and Drug Administration, Cincinnati, OH 45226
1982 - 1984 Visiting Assistant Professor, Department of Foods & Nutrition and Department of Biological Sciences, Purdue University, West Lafayette, IN 47907
1980 - 1982 Postdoctoral Associate (Preceptor Ronald R. Watson, PhD)