MO_I_L: Molecular Sciences I. Lectures
1 Kitti Pázmándi Ph.D., Department of Immunology, Faculty of Medicine, University of Debrecen
2 Tünde Fekete Ph.D., Department of Immunology, Faculty of Medicine, University of Debrecen
Introduction: Plants are a rich source of bioactive phytochemicals, the pharmacological and therapeutic properties of which have been extensively studied lately. The bioactive components of ginger are emerged as potent anti-inflammatory compounds, which are able to exert immunomodulatory effects on different immune cell types. Nevertheless, their effects and mechanism of action has not been explored in human dendritic cells (DCs) yet.
Aim: We investigated how Toll-like receptor (TLR)-mediated responses of human DCs are affected by 6-gingerol and 6-shogaol, which are the major functional compounds of ginger.
Methods: Human monocyte-derived DCs (moDCs) were activated with the TLR4 agonist lipopolysaccharide (LPS) or live Escherichia coli (E. coli) in the presence or absence of 6-gingerol or 6-shogaol. The phenotypical and functional changes of the cells were monitored by flow cytometry, ELISA and western blotting.
Results: We found that the bioactive compounds of ginger significantly decreased the TLR4 activation-induced production of pro-inflammatory cytokines and suppressed the expression of costimulatory and activation markers in moDCs in a concentration dependent manner. The compounds of ginger also suppressed the cytokine producing ability of moDCs upon stimulation with live E.coli. Further, we found that 6-gingerol and 6-shogaol inhibited the TLR4 activation-mediated phosphorylation of IkBα and p65, the members of NF-kB signaling pathway and prevented the phosphorylation of p70S6 kinase and Akt, the major components of mammalian target of rapamycin (mTOR) signaling cascade.
Conclusion: Our results indicate that the major bioactive compounds of ginger interfered with the TLR4-mediated inflammatory responses of human moDCs, probably by inhibiting the NF-κB and mTOR signaling cascades, which are essential for a multitude of functions in DCs. Thus, our results demonstrate that the examined bioactive compounds of ginger exert potent anti-inflammatory and immunomodulatory effects on human DCs.
Funding: NKFIH PD 135193, NKFIH FK 128294, GINOP-2.3.2-15-2016-00050 and EFOP-3.6.3-VEKOP-16-2017-00009 projects, ÚNKP-20-05-DE-3 New National Excellence Program of the Ministry for Innovation and Technology from the source of the National Research, Development and Innovation Fund and the János Bolyai Research Scholarship from the Hungarian Academy of Sciences.
Debrecen University Faculty of Medicine, Doctoral School of Molecular Cell and Immunobiology