Neuroinflammation leads to tissue injury causing many of the clinical symptoms of Multiple Sclerosis, an autoimmune disorder of the central nervous system (CNS). While T cells, specifically T(h)1 and T(h)17 cells, are the ultimate effectors of this disease, dendritic cells (DCs) mediate T cell polarization, activation, etc. In our previous study, Apigenin, a natural flavonoid, has been shown to reduce EAE disease severity through amelioration of demyelination in the CNS as well as the sequestering of DCs and other myeloid cells in the periphery. Here, we show that Apigenin exerts its effects possibly through shifting DC modulated T cell responses from T(h)1 and T(h)17 type towards T(reg)directed responses evident through the decrease in T-bet, IFN-gamma (T(h)1),IL-17 (T(h)17) and increase in IL-10, TGF-beta and FoxP3 (T-reg) expression in cells from both normal human donors and EAE mice. RelB, an NF-kappa beta pathway protein is central to DC maturation, its antigen presentation capabilities and DC-mediated T cell activation. Apigenin reduced mRNA and protein levels of RelB and also reduced its nuclear translocation. Additionally, siRNA-mediated silencing of RelB further potentiated the RelB-mediated effects of Apigenin thus confirming its role in Apigenin directed regulation of DC biology. 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.
Apigenin Modulates Dendritic Cell Activities and Curbs Inflammation Via RelB Inhibition in the Context of Neuroinflammatory Diseases
Creators
Rashida Ginwala - Drexel University
Raina Bhavsar - Drexel University
Patrick Moore - Drexel University
Mariana Bernui - Drexel University
Narendra Sing - Univ South Carolina, Dept Pathol Microbiol & Immunol, Columbia, SC 29208 USA
Frank Bearoff - Drexel University
Mitzi Nagarkatti - Univ South Carolina, Dept Pathol Microbiol & Immunol, Columbia, SC 29208 USA
Zafar K. Khan - Drexel University
Pooja Jain - Drexel University
Publication Details
Journal of neuroimmune pharmacology, v 16(2), pp 403-424
Publisher
Springer Nature
Number of pages
22
Grant note
R01 NS097147 / NIH/NINDS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Neurological Disorders & Stroke (NINDS)
RG 4471A6/2 / National MS Society; National Multiple Sclerosis Society
Resource Type
Journal article
Language
English
Academic Unit
Microbiology and Immunology; Infectious Diseases (and HIV Medicine)
Web of Science ID
WOS:000544613500001
Scopus ID
2-s2.0-85087319781
Other Identifier
991019169666304721
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Collaboration types
Domestic collaboration
Web of Science research areas
Neurosciences
Pharmacology & Pharmacy
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