Platonin is a potent macrophage-activating agent and an immunomodulator. It has been used to treat trauma, ulcers and some acute inflammations. Although platonin has desirable anti-inflammatory effects, its mechanism of action is not clear. In the present study, we investigated the effect of lipopolysaccharide (LPS) on human peripheral blood mononuclear cells (PBMC) gene expression and determined the molecular mechanism of platonin action in the LPS-induced NF-κB signaling pathway.Methods:
In human PBMC, treatments with platonin (0.1 μg/ml) suppressed the production of pro-inflammatory cytokines (IL-1β, TNF-α and IL-6), nitric oxide (NO) and multiple kinases (iNOS, COX-2) induced by LPS. We found that the effect of platonin on LPS-induced production of pro-inflammatory cytokines and multiple kinases was due to the inhibition of NF-κB activity. Additional work revealed that this inhibition was caused by a reduction in the phosphorylation and subsequent degradation of IκBα. Further investigation revealed that Akt and IκB kinase β (IKKβ) activity were also inhibited during platonin treatment, which may be what prevented NF-κB from entering the nucleus and activating gene transcription.Conclusions:
These results suggest the anti-inflammatory activity of platonin is a result of reduced NF-κB activity due to inhibition of Akt and IKKβ.