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A role for stat-1 in regulating interleukin 10 production following LPS challenge

VanDeusen, Jeffrey B
http://rave.ohiolink.edu/etdc/view?acc_num=osu1084860074

Abstract Details

2004, Doctor of Philosophy, Ohio State University, Medical Microbiology and Immunology.
There have been substantial advances in understanding the events that regulate gene expression at the cellular and molecular level, however, there has been limited progress integrating this information to understand how biological systems function in vivo. Complementary DNA and protein microarray technologies in combination with sophisticated bioinformatics may eventually provide important insight into how biologic systems work in vivo. We hypothesized that assessments of such events in vivo would provide new insights into the immune response that could not be predicted or discovered ex vivo. Here, we describe the use of quantitative real time RT-PCR to serially quantify expression of a variety of pro- and anti-inflammatory cytokine genes in a number of individual tissues before, during, and after challenge with lipopolysaccharide (LPS). The data provide new insight into the heterogeneity of cytokine gene expression from organ to organ following infectious insult in vivo, as well as a greater understanding of cytokine regulation. For example, the anti-inflammatory cytokine interleukin-10 (IL-10) is thought to down-regulate the effects of the pro-inflammatory cytokine interferon gamma (IFN-g) on monocyte activation following lipopolysaccharide (LPS) stimulation. However, the often-postulated reciprocal regulation of IL-10 gene expression by IFN-g has not been studied in vivo. Here we serially quantify the expression of IL-10 before, during, and after an in vivo challenge with LPS or a gram-negative organism. In our system, we demonstrate that the regulation of IL-10 gene expression has at least two phases. The early induction occurs independent of the signal transducer and activator of transcription 1 (STAT-1), while a delayed active repression of IL-10 gene expression is critically dependent on STAT-1, most or all of which is independent of IFN-g. Consistent with this, STAT-1 is absent from the IL-10 promoter during the early induction of the cytokine, but is bound to the IL-10 promoter in the delayed repression of the cytokine. Thus, STAT-1 binding to the IL-10 promoter is likely directly associated with STAT-1-mediated repression of IL-10 gene repression during infectious challenge with gram-negative organisms in vivo. This study provides new insights into the regulation of IL-10 following in vivo challenge with a gram-negative organism.
Michael Caligiuri (Advisor)
73 p.
Health Sciences, Immunology
Endotoxic shock; Cytokine Regulation

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Citations

  • VanDeusen, J. B. (2004). A role for stat-1 in regulating interleukin 10 production following LPS challenge [Doctoral dissertation, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu1084860074

    APA Style (7th edition)

  • VanDeusen, Jeffrey. A role for stat-1 in regulating interleukin 10 production following LPS challenge. 2004. Ohio State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=osu1084860074.

    MLA Style (8th edition)

  • VanDeusen, Jeffrey. "A role for stat-1 in regulating interleukin 10 production following LPS challenge." Doctoral dissertation, Ohio State University, 2004. http://rave.ohiolink.edu/etdc/view?acc_num=osu1084860074

    Chicago Manual of Style (17th edition)

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© 2004, all rights reserved.
This open access ETD is published by The Ohio State University and OhioLINK.