| Chen TL |
------>authors3_c= ------>paper_class1=1 ------>Impact_Factor=3.846 ------>paper_class3=2 ------>paper_class2=1 ------>vol=240 ------>confirm_bywho=wslee ------>insert_bywho=rmchen ------>Jurnal_Rank=8.2 ------>authors4_c= ------>comm_author=1 ------>patent_EDate=None ------>authors5_c= ------>publish_day=1 ------>paper_class2Letter=None ------>page2=25 ------>medlineContent= ------>unit=E1300 ------>insert_date=20090616 ------>iam=5 ------>update_date=None ------>author=??? ------>change_event=4 ------>ISSN= ------>authors_c= ------>score=478 ------>journal_name=Toxicology and Applied Pharmacology ------>paper_name=Signal-transducing mechanisms of ketamine-caused inhibition of interleukin-1? gene expression in lipopolysaccharide-stimulated murine macrophage-like Raw 264.7 cells ------>confirm_date=20091105 ------>tch_id=088008 ------>pmid=19540866 ------>page1=15 ------>fullAbstract=Ketamine may affect the host immunity. Interleukin-1 beta (IL-1 beta), IL-6, and tumor necrosis factor-alpha (TNF-alpha) are pivotal cytokines produced by macrophages. This study aimed to evaluate the effects of ketamine on the regulation of inflammatory cytokine gene expression, especially IL-1 beta, in lipopolysaccharide (LPS)-activated murine macrophage-like Raw 264.7 cells and its possible signal-transducing mechanisms. Administration of Raw 264.7 cells with a therapeutic concentration of ketamine (100 microM), LPS, or a combination of ketamine and LPS for 1, 6, and 24 h was not cytotoxic to macrophages. Exposure to 100 microM ketamine decreased the binding affinity of LPS and LPS-binding protein but did not affect LPS-induced RNA and protein synthesis of TLR4. Treatment with LPS significantly increased IL-1 beta, IL-6, and TNF-alpha gene expressions in Raw 264.7 cells. Ketamine at a clinically relevant concentration did not affect the synthesis of these inflammatory cytokines, but significantly decreased LPS-caused increases in these cytokines. Immunoblot analyses, an electrophoretic mobility shift assay, and a reporter luciferase activity assay revealed that ketamine significantly decreased LPS-induced translocation and DNA binding activity of nuclear factor-kappa B (NF kappaB). Administration of LPS sequentially increased the phosphorylations of Ras, Raf, MEK1/2, ERK1/2, and IKK. However, a therapeutic concentration of ketamine alleviated such augmentations. Application of toll-like receptor 4 (TLR4) small interfering (si)RNA reduced cellular TLR4 amounts and ameliorated LPS-induced RAS activation and IL-1 beta synthesis. Co-treatment with ketamine and TLR4 siRNA synergistically ameliorated LPS-caused enhancement of IL-1 beta production. Results of this study show that a therapeutic concentration of ketamine can inhibit gene expression of IL-1 beta possibly through suppressing TLR4-mediated signal-transducing phosphorylations of Ras, Raf, MEK1/2, ERK1/2, and IKK and subsequent translocation and transactivation of NF kappaB. ------>tmu_sno=None ------>sno=21980 ------>authors2=Chang CC ------>authors3=Lin YL ------>authors4=Ueng YF ------>authors5=Chen RM ------>authors6= ------>authors6_c= ------>authors=Chen TL ------>delete_flag=0 ------>SCI_JNo=None ------>authors2_c= ------>publish_area=0 ------>updateTitle=Signal-transducing mechanisms of ketamine-caused inhibition of interleukin-1 beta gene expression in lipopolysaccharide-stimulated murine macrophage-like Raw 264.7 cells. ------>language=2 ------>check_flag=None ------>submit_date=None ------>country=None ------>no= ------>patent_SDate=None ------>update_bywho=None ------>publish_year=2009 ------>submit_flag=None ------>publish_month=10 |