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Myeloid Derived NFκB Regulation of LPS-Induced Endotoxic Shock

Tsai, Yi-Ting
http://rave.ohiolink.edu/etdc/view?acc_num=ucin1393237910

Abstract Details

2013, MS, University of Cincinnati, Medicine: Immunology.
Sepsis is a life-threatening event predominantly caused by gram-negative bacteria. Bacterial infection causes a pronounced macrophages (MΦs) and dendritic cells (DCs) activation which leads to excessive pro-inflammatory cytokine IL-1β, IL-6, and TNFα production (cytokine storm), resulting in endotoxic shock. Previous experimental studies have revealed that inhibition of NFκB signaling ameliorates disease symptoms, however, the contribution of myeloid p65 in endotoxic shock remains elusive. In this study, we demonstrate increased mortality in p65Δmye mice compared to WT mice upon ultra pure LPS (U-LPS) challenge. We show that increased susceptibility to endotoxic shock was associated with elevated serum level of IL-1β and IL-6 and increased recruitment of neutrophils to the peritoneal cavity following U-LPS challenge. Mechanistic analyses revealed that LPS-induced pro-inflammatory cytokine production was ameliorated in p65-deficient non-inflammatory bone marrow-derived macrophages (BMDMs), however, p65-deficient inflammatory peritoneal MPhi;s exhibited elevated IL-1β and IL-6. We show that the elevated IL-1β secretion in part was due to increased caspase-1 expression. Our data demonstrate a differential role of NFκB signaling in non-inflammatory and inflammatory MPhi;s in regulating host response toward LPS challenge and provide an insight to the MΦs/NFκB axis in sepsis.
Simon Hogan, Ph.D. (Committee Chair)
Kasper Hoebe, Ph.D. (Committee Member)
Nives Zimmermann, Ph.D. (Committee Member)
83 p.
Immunology
p65; sepsis; inflammatory; NF kappa B; macrophage; LPS

Recommended Citations

Citations

  • Tsai, Y.-T. (2013). Myeloid Derived NFκB Regulation of LPS-Induced Endotoxic Shock [Master's thesis, University of Cincinnati]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1393237910

    APA Style (7th edition)

  • Tsai, Yi-Ting. Myeloid Derived NFκB Regulation of LPS-Induced Endotoxic Shock. 2013. University of Cincinnati, Master's thesis. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=ucin1393237910.

    MLA Style (8th edition)

  • Tsai, Yi-Ting. "Myeloid Derived NFκB Regulation of LPS-Induced Endotoxic Shock." Master's thesis, University of Cincinnati, 2013. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1393237910

    Chicago Manual of Style (17th edition)

ucin1393237910
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© 2013, all rights reserved.
This open access ETD is published by University of Cincinnati and OhioLINK.