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| author | Tyler J. Dorrity |
| title | Cytokine Responses Generated by cGAMP and other CDNs Depend on Delivery Method |
| abstract |
Cyclic GMP-AMP synthase (cGAS) is an important protein in pattern recognition pathways involving viral DNA. Activated cGAS produces the small molecule 2'3'-cyclic
GMP-AMP (cGAMP) as a second messenger. cGAMP will normally bind to its downstream receptor STING and induce an interferon (IFN) response. In order to understand
cGAMP signaling, THP-1 cells were stimulated with cGAMP with or without viral DNA. Two methods were used to deliver cGAMP to the cells: lipid transfection or
addition straight to the media. Analyses of the cells' responses were completed via qPCR to measure either cGAS or innate immune products IFNb,
ISG56, and IL-1b. It was found that cGAMP delivered to the media repressed expression of cGAS. Untransfected cGAMP also led to repression of
ISG56, while lipid-delivered cGAMP led to increased expression of ISG56. It was hypothesized that this activity of cGAMP was dependent on location
of cyclic dinucleotide (CDN) exposure, inside or outside the cell, which may due to cGAMP's structural similarities to bacterial quorum sensing molecules.
Location-dependent activity of cGAMP was compared to location-dependent activity of other CDNs: c-di-GMP, c-di-AMP, and c-di-UMP. Preliminary results indicate
a trend that CDNs delivered to the media had repressive effects on ISG56. However, this pattern was reversed when IL6, a bacterial immune product,
was measured. The data suggest that there is an extracellular receptor that senses CDNs in addition to the currently known intracellular receptor.
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| school | The College of Liberal Arts, Drew University |
| degree | B.A. (2018) |
| advisor | Brianne Barker |
| committee | Adam Cassano
Christina McKittrick |
| full text |
TJDorrity.pdf
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