Journal article
Toll-like receptor 9 activation with CpG oligodeoxynucleotides for asthma therapy
Drug news & perspectives, Vol.21(8), pp.434-439
10/2008
DOI: 10.1358/dnp.2008.21.8.1272133
PMID: 19034349
Abstract
Prokaryotic DNA has long been recognized as immunostimulatory. In the last decade the role played by CpG motifs (nucleotide sequence motifs centered on a cytosine-guanine dinucleotide) in bacterial and viral DNA has been elucidated. CpG motifs are detected by the innate immune pattern recognition receptor Toll-like receptor (TLR) 9, the ligation of which activates multiple signal cascades in responding cells. A restricted pattern of TLR9 expression to certain dendritic cells and B cells appears to provide relative specificity in responses, especially in comparison to other TLR ligands. TLR9 activation induces a Th1-like pattern of cytokine release which led to interest in the use of synthetic CpG oligodeoxynucleotides (CpG ODN) for the prevention and treatment of Th2-associated atopic disorders such as asthma. Interestingly, Th1 cytokines do not appear to be necessary for a therapeutic response in preclinical models of atopic asthma. Additional potential mechanisms of action include induction of regulatory-type responses (involving interleukin-10 release), and expression of indoleamine 2,3-dioxygenase. CpG ODN have been shown to prevent and reverse antigen-induced eosinophilic airway inflammation in animal models; human trials are ongoing with encouraging early results when used as a ragweed vaccine adjuvant in allergic upper airway disease.
Details
- Title: Subtitle
- Toll-like receptor 9 activation with CpG oligodeoxynucleotides for asthma therapy
- Creators
- Joel N Kline - Department of Medicine, Carver College of Medicine, University of Iowa, Iowa City, Iowa 52242, USA. joel-kline@uiowa.eduArthur M Krieg
- Resource Type
- Journal article
- Publication Details
- Drug news & perspectives, Vol.21(8), pp.434-439
- DOI
- 10.1358/dnp.2008.21.8.1272133
- PMID
- 19034349
- ISSN
- 0214-0934
- eISSN
- 2013-0139
- Grant note
- R01 HL059324 / NHLBI NIH HHS
- Language
- English
- Date published
- 10/2008
- Academic Unit
- Pulmonary, Critical Care, and Occupational Medicine; Occupational and Environmental Health; Internal Medicine
- Record Identifier
- 9984094665702771
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