Foil-like receptor agonists induce apoptosis in mouse 3-cell lymphoma cells by altering NF-κB activation

作     者：Nandini Arunkumar Chaohong Liu Haiying Hang Wenxia Song 

作者机构：Department of Cell Biology & Molecular Genetics University of Maryland College Park Maryland USA National Laboratory of Biomacromolecules Institute of Biophysics Chinese Academy of Sciences Beijing China 

出 版 物：《Cellular & Molecular Immunology》 (中国免疫学杂志（英文版）)

年 卷 期：2013年第10卷第4期

页      面：360-372页

核心收录：

学科分类：090603[农学-临床兽医学] 0710[理学-生物学] 07[理学] 071009[理学-细胞生物学] 09[农学] 0906[农学-兽医学] 0901[农学-作物学] 090102[农学-作物遗传育种] 

基　　金：TheNationalInstituteofHealth,USA(AI059617) Thefundingagencyhadnoroleinthestudydesign,datacollectionandanalysis,decisiontopublish,orpreparationofthemanuscript 

主　　题：apoptosis lymphoma B cells NF-κB Toll-like receptor 

摘      要：Toll-like receptor 9 （TLR9） recognizes microbial DNA containing unmethylated cytosyl guanosyl （CpG） sequences, induces innate immune responses, and facilitates antigen-specific adaptive immunity. Recent studies report that in addition to stimulating innate immunity, TLR9 ligands induce apoptosis of TLR9 expressing cancer cells. To understand the mechanism of TLR9-induced apoptosis, we compared the effects of CpG containing oligodeoxynucleotides （CpG ODN） on a mouse B-cell lymphoma line, CH27, with those on mouse splenic B cells. CpG ODN inhibited constitutive proliferation and induced apoptosis in the CH27 B-cell lymphoma line. In contrast, CpG ODN-treated primary B cells were stimulated to proliferate and were rescued from spontaneous apoptosis. The induction of apoptosis required the ODNs to contain the CpG motif and the expression of TLR9 in lymphoma B cells. A decrease in Bcl-xl expression and an increase in Fas and Fas ligand expression accompanied lymphoma B-cell apoptosis. Treatment with the Fas ligand-neutralizing antibody inhibited CpG ODN-induced apoptosis. CpG ODN triggered a transient NF-κB activation in the B-cell lymphoma cell line, which constitutively expresses a high level of c-Myc, while CpG ODN induced sustained increases in NF-κB activation and c-Myc expression in primary B cells. Furthermore, an NF-κB inhibitor inhibited the proliferation of the CH27 B-cell lymphoma line. Our data suggest that the differential responses of lymphoma and primary B cells to CpG ODN are the result of differences in NF-KB activation. The impaired NF-KB activation in the CpG ODN-treated B-cell lymphoma cell line alters the balance between NF-κB and c-Myc, which induces Fas/Fas ligand-dependent apoptosis.