“Interest-STING”: Inhibition of Innate Immune Signaling by Prostaglandin E2
dc.contributor.author | Mathena, Reilley | |
dc.date.accessioned | 2021-02-05T16:50:57Z | |
dc.date.available | 2021-02-05T16:50:57Z | |
dc.date.issued | 2020 | |
dc.identifier.uri | http://hdl.handle.net/10713/14475 | |
dc.description | Cellular & Molecular Biomedical Sciences | |
dc.description | University of Maryland, Baltimore | |
dc.description | M.S. | |
dc.description.abstract | The cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway senses cytosolic double-stranded DNA from microbial or host cells. cGAS-STING activation elicits an inflammatory response, including production of type I interferons, through activation of TBK1 kinase and the transcription factor IRF3. Therefore, negative regulation of cGAS-STING activity would be predicted to prevent microbial-induced or autoimmune inflammatory damage. Based on prior work, we tested the hypothesis that the inflammatory product prostaglandin E2 (PGE2) acts on immune cells to control inflammation induced by cGAS-STING. STING pathway activating agents, 5,6 dimethylxanthenone-4-acetic acid (DMXAA) and cyclic guanosine monophosphate–adenosine monophosphate (cGAMP), were used to initiate STING signaling. Exogenous PGE2 suppressed DMXAA- and cGAMP-induced STING signaling in murine embryonic fibroblasts and primary murine macrophages. Cells treated with PGE2, followed by DMXAA or cGAMP, exhibited decreased activation of TBK1 and IRF3, and decreased inflammatory gene expression, arguing that PGE2 signaling may be a mechanism restricting cGAS-STING activation. | |
dc.subject | cGAS-STING | |
dc.subject | DMXAA | en_US |
dc.subject.mesh | Immunity--physiology | en_US |
dc.title | “Interest-STING”: Inhibition of Innate Immune Signaling by Prostaglandin E2 | en_US |
dc.type | dissertation | en_US |
dc.date.updated | 2021-01-28T20:07:23Z | |
dc.language.rfc3066 | en | |
dc.contributor.advisor | Vogel, Stefanie N. | |
dc.contributor.orcid | 0000-0002-2049-8139 | en_US |
refterms.dateFOA | 2021-02-05T16:50:58Z |