Specific inhibition of interleukin-10 production in murine macrophage-like cells by phosphorothioate antisense oligonucleotides

被引:8
作者
Arima, H [1 ]
Takahashi, M [1 ]
Aramaki, Y [1 ]
Sakamoto, T [1 ]
Tsuchiya, S [1 ]
机构
[1] Tokyo Univ Pharm & Life Sci, Sch Pharm, Hachioji, Tokyo 19203, Japan
来源
ANTISENSE & NUCLEIC ACID DRUG DEVELOPMENT | 1998年 / 8卷 / 04期
关键词
D O I
10.1089/oli.1.1998.8.319
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The effects of phosphorothioate antisense oligonucleotides (AS-S-oligos) directed against murine interleukin-10 (IL-10) mRNA on IL-10 production in RAW264.7 cells, a murine macrophage-like cell line, when stimulated by lipopolysaccharide (LPS) were examined. Of the six AS-S-oligos used, AS-S-oligos directed against the 3'-untranslated region (3'-UTR) of IL-10 mRNA (AS6-S-oligo) showed the strongest inhibitory effect on IL-10 production, and this inhibition was dose and time dependent. Reverse transcription-polymerase chain reaction (RT-PCR) revealed that the antisense effect originated from a specific reduction of target IL-10 mRNA by hybridization with AS6-S-oligo. In addition, AS6-S-oligo did not affect tumor necrosis factor-alpha (TNF-alpha) production in cells stimulated by LPS, and S-oligos with control sequences did not affect IL-10 production. These findings suggested that AS6-S-oligo most powerfully inhibited IL-10 production in macrophages by an antisense mechanism.
引用
收藏
页码:319 / 327
页数:9
相关论文
共 60 条
[1]   Antisense oligonucleotides: Towards clinical trials [J].
Agrawal, S .
TRENDS IN BIOTECHNOLOGY, 1996, 14 (10) :376-387
[2]   Negatively charged liposomes inhibit tyrosine phosphorylation of 41-kDa protein in murine macrophages stimulated with LPS [J].
Aramaki, Y ;
Matsuno, R ;
Nitta, F ;
Arima, H ;
Tsuchiya, S .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1997, 231 (03) :827-830
[3]  
Ballas ZK, 1996, J IMMUNOL, V157, P1840
[4]  
BARBOUR SE, 1993, J BIOL CHEM, V268, P21875
[5]  
BENNETT CF, 1994, J IMMUNOL, V152, P3530
[6]   The effect of antisense oligodeoxynucleotides on nitric oxide secretion from macrophage-like cells [J].
Bilecki, W ;
Okruszek, A ;
Przevlocki, R .
ANTISENSE & NUCLEIC ACID DRUG DEVELOPMENT, 1997, 7 (06) :531-537
[7]   SELECTION OF SINGLE-STRANDED-DNA MOLECULES THAT BIND AND INHIBIT HUMAN THROMBIN [J].
BOCK, LC ;
GRIFFIN, LC ;
LATHAM, JA ;
VERMAAS, EH ;
TOOLE, JJ .
NATURE, 1992, 355 (6360) :564-566
[8]   THE ANTIPROLIFERATIVE ACTIVITY OF C-MYB AND C-MYC ANTISENSE OLIGONUCLEOTIDES IN SMOOTH-MUSCLE CELLS IS CAUSED BY A NONANTISENSE MECHANISM [J].
BURGESS, TL ;
FISHER, EF ;
ROSS, SL ;
BREADY, JV ;
QIAN, YX ;
BAYEWITCH, LA ;
COHEN, AM ;
HERRERA, CJ ;
HU, SSF ;
KRAMER, TB ;
LOTT, FD ;
MARTIN, FH ;
PIERCE, GF ;
SIMONET, L ;
FARRELL, CL .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1995, 92 (09) :4051-4055
[9]   OLIGODEOXYNUCLEOSIDE PHOSPHOROTHIOATE STABILITY IN SUBCELLULAR EXTRACTS, CULTURE MEDIA, SERA AND CEREBROSPINAL-FLUID [J].
CAMPBELL, JM ;
BACON, TA ;
WICKSTROM, E .
JOURNAL OF BIOCHEMICAL AND BIOPHYSICAL METHODS, 1990, 20 (03) :259-267
[10]  
COHEN L, 1995, J IMMUNOL, V155, P5337