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Dissertation
Potential of the flavonoid Apigenin in regulating immune cell functions during neuroinflammation in a RelB-dependent manner
Doctor of Philosophy (Ph.D.), Drexel University
Dec 2018
DOI:
https://doi.org/10.17918/s9h4-p281
Abstract
Apigenin, a well-documented health promoting agent, belongs to a group of low-molecular weight phyto-pigments called flavonoids that are present ubiquitously in a variety of plants, vegetables and herbs. The chemo-protective effects of Apigenin can be largely attributed towards its anti-inflammatory properties that have been studied in various cell types including the cells of the immune system such as dendritic cells (DCs). DCs are the most potent antigen presenting cells that form an important link between the innate and adaptive branches of the immune system through their ability to capture and present both pathogens and self-antigens and initiate either an immunogenic or tolerogenic response. Any dysregulation in this function causes an immune imbalance leading to disorders that are specially devastating in immune privileged location like the central nervous system. In order to establish the potential utility of Apigenin as a therapeutic agent against neuroinflammatory diseases, we tested and found that Apigenin treatment ameliorated disease severity, progression and relapse of experimental autoimmune encephalomyelitis (EAE) in C57BL/6 and SJL mouse models of multiple sclerosis. An increased retention of DCs and other myeloid cells in the periphery correlated with decreased immune cell infiltration and reduced demyelination in the treated mice. Apigenin possibly exerts its effects through shifting the DC modulated T-cell responses from Th1 and Th17 type towards Th2 and Treg directed responses evident through the decrease in T-bet, IFN-[gamma] (Th1), IL-17 (Th17) and increase in IL-4 (Th2), IL-10, TGF-[beta] and FoxP3 (Treg) expression. Mechanistically, Apigenin treatment reduced cytoplasmic RelB expression in presence of LPS in human peripheral blood DCs, which is central to DC maturation, its antigen presentation capabilities and DC-mediated T cell activation. TNF-[alpha], CD40, and IL-23, downstream targets of RelB were also reduced upon Apigenin treatment in these cells. These results provide key information about the molecular events controlled by Apigenin in its regulation of DC activity marking its potential as a therapy for neuroinflammatory disease.
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Details
- Title
- Potential of the flavonoid Apigenin in regulating immune cell functions during neuroinflammation in a RelB-dependent manner
- Creators
- Rashida Ginwala - DU
- Contributors
- Pooja Jain (Advisor) - Drexel University (1970-)
- Awarding Institution
- Drexel University
- Degree Awarded
- Doctor of Philosophy (Ph.D.)
- Publisher
- Drexel University; Philadelphia, Pennsylvania
- Number of pages
- xiii, 175 pages
- Resource Type
- Dissertation
- Language
- English
- Academic Unit
- School of Biomedical Engineering, Science, and Health Systems (1997-2026); Drexel University
- Other Identifier
- 9331; 991014632209904721