Immunomodulatory Effect of G2013 (α-L-Guluronic Acid) on the TLR2 and TLR4 in Human Mononuclear Cells
2018
Background: Inhibition of Toll-like receptors (TLRs) signaling
have been established as a new method for development of anti-inflammatory
drugs instead of NSAIDs (non-steroid anti-inflammatory drugs). Since the
immunomodulatory role of G2013 was reported in some recent experiments, we
decided to assess the effects of G2013 (a-L-Guluronic acid) on the protein
expression of TLR2 and TLR4, their downstream signaling cascade, and the
secretion of pro-inflammatory cytokines in human peripheral blood
mononuclear cells (PBMCs).
Method: After blood sampling from 16 healthy donors, PBMCs were isolated and
treated with/without lipopolysaccharide (LPS), lipopolyteichoic acid (LTA),
and G2013. Flow cytometry was done for detecting the protein expression of
TLR2 and TLR4. MyD88, IkB, Tollip, and NFkB mRNA expression were
assessed by real-time PCR. ELISA was performed for assessing the
concentration of IL-1β and IL-6.
Results: G2013 at concentration of 25 mg/mL (high dose) significantly
down-regulated NF-κB, IkB and MyD88 mRNA expression and suppressed the
secretion of IL-1β by PBMCs. The findings indicate that G2013 may exert its
regulatory effect under normal condition via Tollip in a dose dependence
pathway. Our results demonstrated that G2013 had no profound impact on the
protein expression of TLR2 and TLR4.
Conclusion: At the conclusion, our findings point to the immunomodulatory
effect of G2013 on the TLR2 and TLR4 signaling cascade and cytokine
production by PBMCs. These findings could lead to establishment of new safe
anti-inflammatory drugs in the future.
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