Date of Graduation
Master of Science in Biology
innate immunity, inflammation, IL-10, LPS, ABIN-3
Macrophages play an important role in the sensing of microbial infection and initiating innate immune responses. The activation of macrophages by pro-inflammatory stimuli, such as bacterial LPS, is mediated through changes in the expression of genes that function to promote inflammation. Pro-inflammatory signaling and gene expression is tightly regulated through the parallel induction of anti-inflammatory genes in response to the host cytokine Interleukin-10 (IL-10). The mechanisms by which IL-10 acts to restrain pro-inflammatory signaling remain incompletely defined. Previously, we identified ABIN-3 as an IL-10-inducible gene capable of inhibiting the action of the pro-inflammatory transcription factor NF-κB in human macrophages. Interestingly, IL-10 can induce expression of ABIN-3 only in macrophages concurrently responding to LPS. Herein, I present studies into the mechanism by which IL-10 synergizes with LPS to induce ABIN-3 gene expression. ABIN-3 falls into the category of a secondary response gene requiring new protein synthesis for its induction in response to IL-10 and LPS. I examined whether the induction of ABIN-3 expression is regulated at the level of transcription or at a post-transcriptional level involving an increase in its mRNA stability. These data indicate that IL-10 synergizes with LPS to induce ABIN-3 gene transcription as opposed to inducing stabilization of its mRNA. Future studies will aim to determine the minimal cis-acting elements within the ABIN-3 gene responsible for its induction by both IL-10 and LPS. These studies should ultimately lead to a better understanding of the crosstalk mechanisms between anti- and pro-inflammatory signaling pathways.
© Brian A. Peterson
Peterson, Brian A., "Regulation of Synergistic Inducible ABIN-3 Gene Expression in Response to IL-10 and LPS" (2010). MSU Graduate Theses. 1281.