Reference - Detail
| RRC ID | 45260 |
|---|---|
| Author | Odkhuu E, Mendjargal A, Koide N, Naiki Y, Komatsu T, Yokochi T. |
| Title | Lipopolysaccharide downregulates the expression of p53 through activation of MDM2 and enhances activation of nuclear factor-kappa B. |
| Journal | Immunobiology |
| Abstract |
The effect of lipopolysaccharide (LPS) on the expression of p53 protein in RAW 264.7 macrophage cells was examined. LPS downregulated the expression of p53 protein 4-24 h after the stimulation. LPS-induced p53 inhibition was restored with pharmacological inhibitors of c-jun N-terminal kinase (JNK) and phosphatidylinositol 3-kinase (PI3K). It was also restored by inhibitors of MDM2 activation and proteasome. LPS-induced p53 inhibition corresponded to activation of MDM2. LPS-induced MDM2 activation was prevented by inhibitors of JNK and PI3K. The expression of p65 NF-κB at a late stage after LPS stimulation was downregulated in the presence of a MDM2 inhibitor. Nutlin-3 as a MDM2 inhibitor reduced LPS-induced production of nitric oxide but not tumor necrosis factor-α. Administration of LPS into mice downregulated the in vivo expression of p53 in the livers. Taken together, LPS was suggested to downregulate the expression of p53 via activation of MDM2 and enhance the activation of NF-κB at a late stage. |
| Volume | 220(1) |
| Pages | 136-41 |
| Published | 2015-1-1 |
| DOI | 10.1016/j.imbio.2014.08.010 |
| PII | S0171-2985(14)00144-2 |
| PMID | 25172547 |
| MeSH | Animals Cell Line Imidazoles / pharmacology Inflammation Mediators / metabolism Lipopolysaccharides / immunology* Lipopolysaccharides / pharmacology Liver / drug effects Liver / immunology Liver / metabolism Macrophages / drug effects Macrophages / immunology Macrophages / metabolism Male Mice NF-kappa B / metabolism* Nitric Oxide / metabolism Phosphatidylinositol 3-Kinases / metabolism Phosphorylation / drug effects Piperazines / pharmacology Protein Binding Protein Kinase Inhibitors / pharmacology Proto-Oncogene Proteins c-akt / metabolism Proto-Oncogene Proteins c-mdm2 / metabolism* Tumor Necrosis Factor-alpha / metabolism Tumor Suppressor Protein p53 / antagonists & inhibitors Tumor Suppressor Protein p53 / genetics Tumor Suppressor Protein p53 / metabolism* |
| IF | 2.788 |
| Times Cited | 11 |
| WOS Category | IMMUNOLOGY |
| Resource | |
| Human and Animal Cells | RAW 264(RCB0535) |