| LDR | | 00000nam u2200205 4500 |
| 001 | | 000000432524 |
| 005 | | 20200224131847 |
| 008 | | 200131s2019 ||||||||||||||||| ||eng d |
| 020 | |
▼a 9781088336755 |
| 035 | |
▼a (MiAaPQ)AAI13902402 |
| 040 | |
▼a MiAaPQ
▼c MiAaPQ
▼d 247004 |
| 082 | 0 |
▼a 576 |
| 100 | 1 |
▼a DeLaney, Alexandra Anne. |
| 245 | 14 |
▼a The Mechanism of Caspase-8-Mediated Gene Expression and Its Integral Role in Host Defense. |
| 260 | |
▼a [S.l.]:
▼b University of Pennsylvania.,
▼c 2019. |
| 260 | 1 |
▼a Ann Arbor:
▼b ProQuest Dissertations & Theses,
▼c 2019. |
| 300 | |
▼a 202 p. |
| 500 | |
▼a Source: Dissertations Abstracts International, Volume: 81-04, Section: B. |
| 500 | |
▼a Advisor: Brodsky, Igor E. |
| 502 | 1 |
▼a Thesis (Ph.D.)--University of Pennsylvania, 2019. |
| 506 | |
▼a This item must not be sold to any third party vendors. |
| 506 | |
▼a This item must not be added to any third party search indexes. |
| 520 | |
▼a Caspase-8 is a key integrator of cell survival and cell death decisions during infection and inflammation. Additionally, caspase-8 has an important, but less understood, role in cell-intrinsic inflammatory gene expression. Macrophages lacking caspase-8 have defective inflammatory cytokine expression in response to bacterial infection or TLR stimulation. How caspase-8 regulates cytokine gene expression, and whether caspase-8-mediated gene regulation has a physiological role during infection remains poorly defined. In this thesis we demonstrate that both caspase-8 enzymatic activity and scaffolding functions play a role in control of inflammatory cytokine gene expression. Caspase-8 enzymatic activity mediates IKK phosphorylation and nuclear translocation of the NF-觀B family member c-Rel to promote maximal expression of Il1b and Il12b. Overexpression of c-Rel was sufficient to restore expression of IL-12 and IL-1棺 in caspase-8-deficient cells. Moreover, the cytokine regulatory function of caspase-8 promoted host survival during infection by the intracellular parasite Toxoplasma gondii. Caspase-8-deficient mice displayed acute mortality during T. gondii infection and a defect in intracellular IL-12 production by DCs. Exogenous IL-12 promoted complete survival of caspase-8-deficient mice during acute toxoplasmosis. Our findings provide new insight into how caspase-8 controls inflammatory gene expression and, for the first time, identify a critical role for caspase-8 in host defense against a eukaryotic pathogen. |
| 590 | |
▼a School code: 0175. |
| 650 | 4 |
▼a Molecular biology. |
| 650 | 4 |
▼a Immunology. |
| 650 | 4 |
▼a Microbiology. |
| 690 | |
▼a 0307 |
| 690 | |
▼a 0982 |
| 690 | |
▼a 0410 |
| 710 | 20 |
▼a University of Pennsylvania.
▼b Cell and Molecular Biology. |
| 773 | 0 |
▼t Dissertations Abstracts International
▼g 81-04B. |
| 773 | |
▼t Dissertation Abstract International |
| 790 | |
▼a 0175 |
| 791 | |
▼a Ph.D. |
| 792 | |
▼a 2019 |
| 793 | |
▼a English |
| 856 | 40 |
▼u http://www.riss.kr/pdu/ddodLink.do?id=T15492363
▼n KERIS
▼z 이 자료의 원문은 한국교육학술정보원에서 제공합니다. |
| 980 | |
▼a 202002
▼f 2020 |
| 990 | |
▼a ***1008102 |
| 991 | |
▼a E-BOOK |