A novel lipopolysaccharide-antagonizing aptamer protects mice against endotoxemia

被引：19

作者：

Wen, Ai-qing ^{[1
]}

Yang, Qing-wu ^{[1
]}

Li, Jing-cheng ^{[1
]}

Lv, Feng-ling ^{[2
]}

Zhong, Qi ^{[1
]}

Chen, Cai-yu ^{[1
]}

机构：

[1] Third Mil Med Univ, Daping Hosp, Dept Neurol, Chongqing 400042, Peoples R China

[2] Chongqing Univ, Coll Biomed Engn, Chongqing 400047, Peoples R China

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2009年 / 382卷 / 01期

基金：

中国国家自然科学基金;

关键词：

Lipopolysaccharide; Aptamers; Septic shock; Proinflammatory; SELEX; SEPTIC SHOCK; SEVERE SEPSIS; RNA APTAMERS; OLIGONUCLEOTIDES; MULTICENTER; BLOCKS; E5531;

D O I：

10.1016/j.bbrc.2009.02.152

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：

A growing number of researchers have recognized the importance of using lipopolysaccharide (LPS) as target for the prevention and treatment of sepsis. However, no drugs targeting LPS have been applied clinically. In this study, LPS-inhibiting aptamers were screened by Systematic Evolution of Ligands by Exponential Enrichment (SELEX), and their therapeutic effects for experimental sepsis were observed. After 12 rounds of screening, 46 sequences were obtained. Primary structure analysis indicated that they had identical sequences, partly conserved sequences, or non-conserved sequences. Secondary Structure analysis showed these sequences usually contained hairpin or stem-loop structures. Aptamer 19 significantly decreased NF-kappa B activation of monocytes challenged by LPS and reduced the IL-1 and TNF-alpha concentration in the media of LPS-challenged monocytes. Furthermore, aptamer 19 significantly increased the Survival rate of mice with endotoxemia. The results suggest that a novel LPS antagonizing aptamer was obtained by SELEX, which successfully treated experimental sepsis. (C) 2009 Elsevier Inc. All rights reserved.

引用

页码：140 / 144

页数：5

共 27 条

[1] A 2ND LARGE CONTROLLED CLINICAL-STUDY OF E5, A MONOCLONAL-ANTIBODY TO ENDOTOXIN - RESULTS OF A PROSPECTIVE, MULTICENTER, RANDOMIZED, CONTROLLED TRIAL [J].

BONE, RC ;

BALK, RA ;

FEIN, AM ;

PERL, TM ;

WENZEL, RP ;

REINES, HD ;

QUENZER, RW ;

IBERTI, TJ ;

MACINTYRE, N ;

SCHEIN, RMH ;

TRENHOLME, G ;

NIEDERMAN, M ;

CHALFIN, D ;

ABALOS, A ;

OROPELLO, J ;

EMPSON, P ;

CAMINITII, S ;

GREENMAN, R ;

BOOTH, F ;

PLOUFFE, J ;

RUSSELL, J ;

GIANAKOPOULOS, G ;

IANNINI, P ;

HINDES, R ;

COBLENS, K ;

KOHLER, R ;

MARTIN, M ;

BERNARD, G ;

EDWARDS, J ;

CRISLIP, M ;

FILLER, S ;

NASRAWAY, SA ;

SIGEL, PK ;

SOTTILE, FD ;

MARTIN, DH ;

DEBOISBLANC, BP ;

CHANDRASEKAR, PH ;

BROUGHTON, WA ;

MIDDLETON, RM ;

SEIBERT, AF ;

EMMANUEL, G ;

LIE, TH ;

ANDERSON, CLV ;

PANKEY, GA ;

ANDERSON, P ;

OLSEN, K ;

SANPEDRO, GS ;

GRAHAM, D ;

GROSSMAN, J ;

WELS, PB .

CRITICAL CARE MEDICINE, 1995, 23 (06) :994-1006

[2] The epidemiology of the systemic inflammatory response [J].

Brun-Buisson, C .

INTENSIVE CARE MEDICINE, 2000, 26 (Suppl 1) :S64-S74

[3] INCIDENCE, RISK-FACTORS, AND OUTCOME OF SEVERE SEPSIS AND SEPTIC SHOCK IN ADULTS - A MULTICENTER PROSPECTIVE-STUDY IN INTENSIVE-CARE UNITS [J].

BRUNBUISSON, C ;

DOYON, F ;

CARLET, J ;

DELLAMONICA, P ;

GOUIN, F ;

LEPOUTRE, A ;

MERCIER, JC ;

OFFENSTADT, G ;

REGNIER, B .

JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 1995, 274 (12) :968-974

[4] A lipid A analog, E5531, blocks the endotoxin response in human volunteers with experimental endotoxemia [J].

Bunnell, E ;

Lynn, M ;

Habet, K ;

Neumann, A ;

Perdomo, CA ;

Friedhoff, LT ;

Rogers, SL ;

Parrillo, JE .

CRITICAL CARE MEDICINE, 2000, 28 (08) :2713-2720

[5] Potent inhibition of human influenza H5N1 virus by oligonucleotides derived by SELEX [J].

Cheng, Congsheng ;

Dong, Jie ;

Yao, Lihong ;

Chen, Aijun ;

Jia, Runqing ;

Huan, Lifang ;

Guo, Jianqlang ;

Shu, Yuelong ;

Zhang, Zhiqing .

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2008, 366 (03) :670-674

[6] E5531, A PURE ENDOTOXIN ANTAGONIST OF HIGH POTENCY [J].

CHRIST, WJ ;

ASANO, O ;

ROBIDOUX, ALC ;

PEREZ, M ;

WANG, YA ;

DUBUC, GR ;

GAVIN, WE ;

HAWKINS, LD ;

MCGUINNESS, PD ;

MULLARKEY, MA ;

LEWIS, MD ;

KISHI, Y ;

KAWATA, T ;

BRISTOL, JR ;

ROSE, JR ;

ROSSIGNOL, DP ;

KOBAYASHI, S ;

HISHINUMA, L ;

KIMURA, A ;

ASAKAWA, N ;

KATAYAMA, K ;

YAMATSU, I .

SCIENCE, 1995, 268 (5207) :80-83

[7] 2′-O-Methyl-RNA hairpins generate loop-loop complexes and selectively inhibit HIV-1 Tat-mediated transcription [J].

Darfeuille, F ;

Arzumanov, A ;

Gait, MJ ;

Di Primo, C ;

Toulmé, JJ .

BIOCHEMISTRY, 2002, 41 (40) :12186-12192

[8]

Downey Jocelyn S., 1998, Frontiers in Bioscience, V3, pD468

[9] Pharmacokinetics and safety of an anti-vascular endothelial growth factor aptamer (NX1838) following injection into the vitreous humor of rhesus monkeys [J].

Drolet, DW ;

Nelson, J ;

Tucker, CE ;

Zack, PM ;

Nixon, K ;

Bolin, R ;

Judkins, MB ;

Farmer, JA ;

Wolf, JL ;

Gill, SC ;

Bendele, RA .

PHARMACEUTICAL RESEARCH, 2000, 17 (12) :1503-1510

[10]

Drolet DW, 1999, COMB CHEM HIGH T SCR, V2, P271

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