Document Detail

Suppressive oligodeoxynucleotides inhibit CpG-induced inflammation of the mouse lung.
MedLine Citation:
PMID:  15483413     Owner:  NLM     Status:  MEDLINE    
OBJECTIVE: To examine the effect of suppressive oligodeoxynucleotides (ODNs) on the pulmonary inflammation induced by immunostimulatory CpG DNA. DESIGN: Prospective, randomized, controlled study. SETTING: Research laboratories. SUBJECTS: RAW 264.7 murine macrophage-like cell line and BALB/c mice. INTERVENTIONS: RAW 264.7 cells were incubated with bacterial DNA or CpG ODN, alone or combined with suppressive ODN. The in vivo effect of suppressive ODN was determined using an acute lung injury model. CpG ODN alone or combined with suppressive ODN was instilled into the mouse lung. MEASUREMENTS AND MAIN RESULTS: Production of tumor necrosis factor (TNF)-alpha and macrophage inflammatory protein (MIP)-2 by RAW 264.7 cells were measured by enzyme-linked immunosorbent assay (ELISA), whereas their messenger RNA levels were determined by reverse transcriptase-polymerase chain reaction. Synthetic ODN containing CpG motifs (CpG ODN) mimicked the ability of bacterial DNA to stimulate the production of TNF-alpha and MIP-2. Suppressive ODN significantly inhibited the activation of RAW 264.7 cells by both bacterial DNA and CpG ODN. In the lung injury model, production of proinflammatory cytokines (TNF-alpha and IL-6) and chemokines (MIP-2 and KC) in bronchoalveolar lavage (BAL) fluids was measured by ELISA. Neutrophil accumulation in the alveolar spaces was also evaluated. Instillation of CpG ODN into the lungs of normal mice triggered the synthesis of TNF-alpha, IL-6, MIP-2, and KC. Suppressive ODN significantly blocked the production of these proinflammatory cytokines and chemokines and also reduced neutrophil mobilization into the alveolar spaces by CpG DNA. CONCLUSIONS: Proinflammatory cytokines and chemokines are up-regulated by CpG motifs in bacterial DNA. Suppressive ODN significantly inhibits the inflammatory response induced by CpG DNA in murine macrophages and the lung. This study supports the use of suppressive ODN to reduce the deleterious inflammatory responses induced by bacterial DNA.
Hiroshi Yamada; Ken J Ishii; Dennis M Klinman
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Publication Detail:
Type:  Evaluation Studies; Journal Article    
Journal Detail:
Title:  Critical care medicine     Volume:  32     ISSN:  0090-3493     ISO Abbreviation:  Crit. Care Med.     Publication Date:  2004 Oct 
Date Detail:
Created Date:  2004-10-14     Completed Date:  2004-11-19     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  0355501     Medline TA:  Crit Care Med     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2045-9     Citation Subset:  AIM; IM    
Department of Anesthesiology, Yokohama City University, School of Medicine, Japan.
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MeSH Terms
Adjuvants, Immunologic / pharmacology
Bronchoalveolar Lavage Fluid / chemistry,  immunology
Cell Line
Chemokine CXCL2
Chemotaxis, Leukocyte / drug effects,  immunology
CpG Islands / drug effects,  immunology*
DNA, Bacterial / immunology*,  pharmacology
Lung / drug effects*,  immunology
Mice, Inbred BALB C
Models, Animal
Monokines / biosynthesis
Oligodeoxyribonucleotides / immunology,  pharmacology*
Pneumonia / immunology*
Prospective Studies
Respiratory Distress Syndrome, Adult / immunology
Tumor Necrosis Factor-alpha / biosynthesis
Reg. No./Substance:
0/Adjuvants, Immunologic; 0/CPG-oligonucleotide; 0/Chemokine CXCL2; 0/DNA, Bacterial; 0/Monokines; 0/Oligodeoxyribonucleotides; 0/Tumor Necrosis Factor-alpha

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