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| Status |
Public on Aug 07, 2018 |
| Title |
Casp8- and Casp11-dependent gene expression in ileal mucosa of LPS-challenged male mice |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
The execution of shock following high dose E. coli lipopolysaccharide (LPS) or bacterial sepsis in mice required pro-apoptotic caspase-8 in addition to pro-pyroptotic caspase-11 and gasdermin d. Hematopoietic cells produced MyD88- and TRIF-dependent inflammatory cytokines sufficient to initiate LPS shock independent of caspase-8 or caspase-11. Both proteases had to be present to support tissue injury, dependent upon TNF and interferon , first observed in the small intestine and later in spleen and thymus. Caspase-11 enhanced the activation of caspase-8 and extrinsic cell death machinery within the lower small intestine. Neither caspase-8 nor caspase-11 was individually sufficient for shock, but collaborated to amplify the inflammatory signals associated with tissue injury. Therefore, combined pyroptotic and apoptotic signaling mediated endotoxemia independent of RIPK1 kinase activity and RIPK3 function. These observations bring to light the relevance of tissue compartmentalization during inflammatory signaling in vivo where cytokines execute diverse cell death pathways and tissue damage.
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| Overall design |
Ileum was harvested from Wt (C57BL/6), Casp8-RIPK3-deficient and Casp11-deficient mice (5 male for each group) at 1.5 h post challenge with high dose LPS (54 mg/kg). Excised tissues were maintained in RNAlater solution for 24 h and RNA was harvested from mucosa.
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| Contributor(s) |
Mandal P, Mocarski ES, Bosinger SE, Patel N, Tharp GK |
| Citation(s) |
30021146 |
| |
| Submission date |
May 30, 2018 |
| Last update date |
Feb 11, 2019 |
| Contact name |
Gregory K Tharp |
| E-mail(s) |
gktharp@emory.edu
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| Phone |
404-727-7797
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| Organization name |
Yerkes National Primate Research Center
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| Department |
Developmental and Cognitive Neuroscience
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| Lab |
Genomics Core
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| Street address |
954 Gatewood Dr
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| City |
Atlanta |
| State/province |
GA |
| ZIP/Postal code |
30329-4208 |
| Country |
USA |
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| Platforms (1) |
| GPL21493 |
Illumina HiSeq 3000 (Mus musculus) |
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| Samples (15)
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| Relations |
| BioProject |
PRJNA473781 |
| SRA |
SRP149344 |
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