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The Mechanism of Caspase-8-Mediated Gene Expression and Its Integral Role in Host Defense
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| 자료유형 | 학위논문 |
|---|---|
| 서명/저자사항 | The Mechanism of Caspase-8-Mediated Gene Expression and Its Integral Role in Host Defense. |
| 개인저자 | DeLaney, Alexandra Anne. |
| 단체저자명 | University of Pennsylvania. Cell and Molecular Biology. |
| 발행사항 | [S.l.]: University of Pennsylvania., 2019. |
| 발행사항 | Ann Arbor: ProQuest Dissertations & Theses, 2019. |
| 형태사항 | 202 p. |
| 기본자료 저록 | Dissertations Abstracts International 81-04B. Dissertation Abstract International |
| ISBN | 9781088336755 |
| 학위논문주기 | Thesis (Ph.D.)--University of Pennsylvania, 2019. |
| 일반주기 |
Source: Dissertations Abstracts International, Volume: 81-04, Section: B.
Advisor: Brodsky, Igor E. |
| 이용제한사항 | This item must not be sold to any third party vendors.This item must not be added to any third party search indexes. |
| 요약 | 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. |
| 일반주제명 | Molecular biology. Immunology. Microbiology. |
| 언어 | 영어 |
| 바로가기 | 
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