Cytosine-phosphate-guanine (CpG) motifs are sensitizing agents for lipopolysaccharide in toxic shock model

Cornélie, Sylvie; Wiel, É.; Lund, N.; Lebuffe, Gilles; Vendeville, Catherine; Riveau, Gilles; Vallet, B.; Ban, Elisabeth

doi:10.1007/s00134-002-1418-z

Cited by 30 publications

(45 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In this model system, administration of immunostimulatory CpG ODN reduced survival (Fig. 1C), a finding consistent with the ability of CpG DNA to synergistically enhance LPS-induced cytokine production (29,30).…”

Section: Suppressive Odn A151 Protects Mice From Lps-induced Endotoxisupporting

confidence: 79%

Suppressive Oligodeoxynucleotides Protect Mice from Lethal Endotoxic Shock

Shirota

Gürsel

et al. 2005

The Journal of Immunology

122

View full text Add to dashboard Cite

Endotoxic shock is a life-threatening condition caused by exposure to bacterial LPS. LPS triggers the release of acute phase, proinflammatory, and Th1 cytokines that facilitate the development of endotoxic shock. Synthetic oligodeoxynucleotides (ODN) expressing suppressive TTAGGG motifs effectively down-regulate the production of proinflammatory and Th1 cytokines elicited by a variety of immune stimuli. The current results demonstrate that suppressive ODN protect mice from LPS-induced endotoxic shock. Underlying this protective effect is the ability of suppressive ODN to bind to and prevent the phosphorylation of STAT1 and STAT4, thereby blocking the signaling cascade mediated by LPS-induced IFN-β and IL-12. These findings suggest that suppressive ODN might be of use in the treatment of endotoxic shock.

show abstract

Section: Suppressive Odn A151 Protects Mice From Lps-induced Endotoxisupporting

confidence: 79%

Suppressive Oligodeoxynucleotides Protect Mice from Lethal Endotoxic Shock

Shirota

Gürsel

et al. 2005

The Journal of Immunology

122

View full text Add to dashboard Cite

show abstract

“…Klebsiella. Importantly, although potentially beneficial in systemic infections, deleterious effects can occur when bacterial DNA or CpG ODN is administered in a systemic fashion (3,21,36,37). In our model, the compartmentalized delivery of CpG ODN was well tolerated and may be preferable to systemic delivery methods when protecting against respiratory pathogens.…”

Section: Discussionmentioning

confidence: 86%

CpG Oligodeoxynucleotides Stimulate Protective Innate Immunity against PulmonaryKlebsiellaInfection

Deng

Moore

Newstead

et al. 2004

The Journal of Immunology

View full text Add to dashboard Cite

Bacterial pneumonia is a leading cause of mortality in the United States. Innate immune responses, including type-1 cytokine production, are critical to the effective clearance of bacterial pathogens from the lung. Synthetic oligodeoxynucleotides (ODN) containing unmethylated CpG dinucleotide motifs (CpG ODN), which mimic the effects of bacterial DNA, have been shown to enhance type-1 cytokine responses during infection due to intracellular pathogens, resulting in enhanced microbial clearance. The role of CpG ODN in modulating protective innate immunity against extracellular pathogens is unknown. Using a murine model of Gram-negative pneumonia, we found that CpG ODN administration stimulated protective immunity against Klebsiella pneumoniae. Specifically, intratracheal (i.t.) administration of CpG ODN (30 μg) 48 h before i.t. K. pneumoniae challenge resulted in increased survival, compared with animals pretreated with control ODN or saline. Pretreatment with CpG ODN resulted in enhanced bacterial clearance in lung and blood, and higher numbers of pulmonary neutrophils, NKT cells, γδ-T cells, and activated NK1.1+ cells and γδ-T lymphocytes during infection. Furthermore, pretreatment with CpG ODN enhanced the production of TNF-α, and type-1 cytokines, including IL-12, IFN-γ, and the IFN-γ-dependent ELR− CXC chemokines IFN-γ-inducible protein-10 and monokine induced by IFN-γ in response to Klebsiella challenge, compared with control mice. These findings indicate that i.t. administration of CpG ODN can stimulate multiple components of innate immunity in the lung, and may form the basis for novel therapies directed at enhancing protective immune responses to severe bacterial infections of the lung.

show abstract

“…On the other hand, Table 2 Bile flow and liver enzyme activities at 6 and 16 h after LPS-exposure in control-ODN-and CpG-ODN pre-treated animals Bile flow (ml/min g) AST (U/L) ALT (U/L) LDH (U/L) Values are given as meanGSEM. others have shown that the synergistic enhancement of LPSmediated TNF-a production by CpG-ODN [26][27][28] increases the toxicity and mortality after endotoxin exposure [16,28,29]. However, CpGs, in particular if applied before LPS stimulation, have also been shown to be capable of reducing LPS-mediated NFkB activation [30] and TNF-a production in vitro [31,32], and minimizing LPS-induced inflammation in the lower respiratory tract in vivo [33].…”

Section: Discussionmentioning

confidence: 98%

Immunostimulatory CpG-oligodeoxynucleotides (CpG-ODN) induce early hepatic injury, but provide a late window for protection against endotoxin-mediated liver damage

Slotta

Scheuer

Menger

et al. 2006

Journal of Hepatology

View full text Add to dashboard Cite

Cytosine-phosphate-guanine (CpG) motifs are sensitizing agents for lipopolysaccharide in toxic shock model

Abstract: Our findings indicate that CpG motifs act synergistically with LPS by initializing the synthesis of TNF-alpha and/or TNF-alpha regulating factors, thereby acting as a sensitizing agent.

Cited by 30 publications

References 46 publications

Suppressive Oligodeoxynucleotides Protect Mice from Lethal Endotoxic Shock

Suppressive Oligodeoxynucleotides Protect Mice from Lethal Endotoxic Shock

CpG Oligodeoxynucleotides Stimulate Protective Innate Immunity against PulmonaryKlebsiellaInfection

Immunostimulatory CpG-oligodeoxynucleotides (CpG-ODN) induce early hepatic injury, but provide a late window for protection against endotoxin-mediated liver damage

Contact Info

Product

Resources

About