Potential of the Flavonoid Apigenin in Regulating Immune Cell Functions
Thursday, November 30, 2017
10:00 AM-12:00 PM
BIOMED PhD Research Proposal
Potential of the Flavonoid Apigenin in Regulating Immune Cell Functions During Neuroinflammation in a RelB-dependent Manner
Rashida Ginwala, PhD Candidate, School of Biomedical Engineering, Science and Health Systems
Pooja Jain, PhD, Professor, Department of Microbiology and Immunology, College of Medicine, Drexel University
Adrian Shieh, PhD, Associate Professor, School of Biomedical Engineering, Science and Health Systems, Drexel University
Apigenin, a natural flavonoid found in several plants, is known to have anti-oxidant and anti-inflammatory properties; however, its effect on dendritic cell (DC) function in maintaining an immune balance in an immunospecialized location like the central nervous system (CNS) is not well-studied.
To establish the potential utility of Apigenin as a therapeutic agent against neuroinflammatory diseases, we tested and found that Apigenin treatment ameliorated severity of disease progression and relapse after onset of experimental autoimmune encephalomyelitis (EAE) in C57BL/6 and SJL mouse models of multiple sclerosis. Apigenin treated EAE mice showed decreased expression of α4 integrin (adhesion) and CLEC12A (antigen uptake) on splenic DCs. An increased retention of DCs and other myeloid cells in the periphery correlated with decreased immune cell infiltration and reduced demyelination in the CNS.
Additionally, both ex vivo antigen-dependent and antigen-independent immune cell responses were modulated by Apigenin with distinct polarization towards a regulatory phenotype. 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-α and IL-23, downstream targets of RelB were also reduced upon Apigenin treatment in these cells. RelB also plays a role in mitochondrial bioenergetics during inflammation, which explains the metabolic shift away from glycolysis observed upon Apigenin treatment in the inflamed DCs. These results indicate a protective role of Apigenin against neurodegenerative DC-regulated effects through a probable RelB mediated pathway thus implicating a potential therapy for neuroinflammatory disease.