Effects of adenoviral gene transfer of mutated IκBα,a novel inhibitor of NF-κB,on human monocyte-derived dendritic cells
Effects of adenoviral gene transfer of mutated IκBα,a novel inhibitor of NF-κB,on human monocyte-derived dendritic cells作者机构：Department of Respiratory Medicine the First Affiliated Hospital Nanjing Medical University Nanjing China Department of Microbiology and Immunology Nanjing Medical University Nanjing China Atheroscleorosis Research Center Nanjing Medical University Nanjing China
出 版 物：《Acta Pharmacologica Sinica》 (中国药理学报(英文版))
年 卷 期：2006年第27卷第5期
页 面：609-616页
核心收录：
学科分类：1007[医学-药学(可授医学、理学学位)] 1006[医学-中西医结合] 100706[医学-药理学] 100602[医学-中西医结合临床] 10[医学]
基 金：Project supported by grants from the National Youth Natural Science Foundation of China(No 30400191) National Natural Science Foundation of China(No 30570797) the Key Subject of Project “135” of Jiangsu Province(No 20013102)
主 题：dendritic cells nuclear factor κB IκBαmutant immunotherapy asthma
摘 要：Aim:To investigate the effects of adenoviral gene transfer of IκBα mutant (IκBαM),a novel inhibitor of nuclear factor κB(NF-κB),on apoptosis,phenotype and func-tion of human monocyte-derived dendritic cells (DC).Methods:Monocytes,cocultured with granulocyte/macrophage colony-stimulating factor (GM-CSF;900ng/mL) and interleukin (IL)-4 (300ng/mL) for 5d,followed by stimulation withlipopolysaccharide (LPS;100ng/mL) for 2d differentiated into mature ***-cytes were either left untransfected or were transfected with AdIκBαM or *** transcription and expression of the IκBαM gene,and the inhibitory effect ofIκBαM on tumor necrosis factor (TNF)-α-induced NF-κB activation in mature DCwere detected by polymerase chain reaction (PCR),reverse transcription-poly-merase chain reaction (RT-PCR),Western blot analysis,and electrophoretic mobil-ity shift assays,*** phenotype,apoptosis,IL-12 secretion level ofDC,and ability to stimulate the proliferation of T cells were determined by flowcytometry,enzyme-linked immunosorbent assay and mixed leukocyte ***:PCR and RT-PCR were used to detect a unique 801 bp band in AdIκBαM-transfected mature DC,and also a dose-and time-dependent expression of theIκBαM gene,which peaked at a multiplicity of infection of 100pfu/cell and at ***,AdIκBαM significantly suppressed the TNF-α-induced NF-κBactivation,augmented apoptosis,downregulated CD80,CD83,and CD86 surfacemolecules,IL-12 secretion levels and the ability to stimulate the proliferation of Tcells in mature ***:AdIκBαM effectively transfected and potentlyinhibited NF-κB activation in monocyte-derived mature *** ofthe IκBαM gene in mature DC may contribute to T-cell immunosuppression throughinduction of DC apoptosis and downregulation of B7 molecules,providing a po-tential strategy for future DC-based immunotherapy of asthma.
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