Platonin inhibits LPS-induced NF-kappaB by preventing activation of Akt and IKKbeta in human PBMC.

OBJECTIVE: 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-kappaB signaling pathway.

METHODS: In human PBMC, treatments with platonin (0.1 microg/ml) suppressed the production of pro-inflammatory cytokines (IL-1beta, TNF-alpha 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-kappaB activity. Additional work revealed that this inhibition was caused by a reduction in the phosphorylation and subsequent degradation of IkappaBalpha. Further investigation revealed that Akt and IkappaB kinase beta (IKKbeta) activity were also inhibited during platonin treatment, which may be what prevented NF-kappaB from entering the nucleus and activating gene transcription.

CONCLUSIONS: These results suggest the anti-inflammatory activity of platonin is a result of reduced NF-kappaB activity due to inhibition of Akt and IKKbeta.