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.
Shao
D Z
DZ
Department of Cosmetics Application and Management, Chung Hwa University of Medical Technology, 89 Wenhwa 1st St., Tainan, Taiwan. dzshao@mail.hwai.edu.tw
Lin
M
M
D051546:Cyclooxygenase 2 / Q000378:metabolism; D004789:Enzyme Activation; D006801:Humans; D051550:I-kappa B Kinase / Q000378:metabolism*; D020672:I-kappa B Proteins / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism; D008070:Lipopolysaccharides / Q000276:immunology*; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D013844:Thiazoles / Q000276:immunology / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D020672:I-kappa B Proteins; D053583:Interleukin-1beta; D015850:Interleukin-6; D008070:Lipopolysaccharides; D016328:NF-kappa B; C000606204:NFKBIA protein, human; D013844:Thiazoles; D014409:Tumor Necrosis Factor-alpha; C032149:platonin; D000072000:NF-KappaB Inhibitor alpha; D009569:Nitric Oxide; C496319:NOS2 protein, human; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D051057:Proto-Oncogene Proteins c-akt; D051550:I-kappa B Kinase