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Immunomodulatory effect of cytosine-phosphate-guanosine (CpG)-oligonucleotides in nonasthmatic chronic rhinosinusitis: an explant model

Immunomodulatory effect of cytosine-phosphate-guanosine (CpG)-oligonucleotides in nonasthmatic chronic rhinosinusitis: an explant model

Authors :
Leonie Baker
Nick Hatzirodos
Trisha J. Rogers
Peter-John Wormald
Enghooi Ooi
Lorwai Tan
Tan, Lorwai
Rogers, Trisha J
Hatzirodos, Nick
Baker, Leonie M
Ooi, Enghooi
Wormald, Peter-John
Source :
American journal of rhinologyallergy. 23(2)
Publication Year :
2009

Abstract

BackgroundThe use of cytosine-phosphate-guanosine-oligodeoxynucleotides (CpG-ODNs) or immunostimulatory sequences (ISSs) in the treatment of airway diseases is gaining interest. Binding of the CpG-ODN ligand to Toll-like receptor 9 (TLR9) triggers a shift from a Th2- to a Th1-type response in the target tissue. In this study, we explored the potential use of CpG-ODN to dampen the predominantly Th2-driven chronic inflammatory state in our cohort of patients.MethodsAn in vitro explant model comprising of sinonasal tissue from patients with asthma (n = 12) and without asthma (n = 11) were stimulated with CpG-ODN or Staphylococcus aureus enterotoxin B (SEB) or CpG-ODN in combination with SEBfor 48 hours. Ten of the 12 asthma patients had nasal polyps. RNA was extracted for multiplex real-time reverse transcription polymerase chain reaction analysis and the 2−delta deltaCTmethod used to determine interleukin (IL)-5, p35 IL-12, interferon (IFN) gamma, and TLR9 expression levels.ResultsCpG-ODN significantly reduced IL-5 mRNA expression in patients without asthma (p = 0.0379) but not in the asthma-associated group. SEB alone caused an increase in IL-5 levels that could be dampened when CpG-ODN was added in combination with SEB. Significant differences in mean IL-5 expression levels between the asthmatic and nonasthmatic categories were detected (Welch t-test;**p = 0.0041). Asthmatic and nonasthmatic patients present as two distinct categories as reflected by significant differences in their IL-5 response to CpG-ODN (F = 11.93;***p = 0.0008), SEB (F = 41.34;*p = 0.0476) and CpG-ODN with SEB (F = 13.2;*p = 0.0114). In contrast, no significant differences were observed in the expression levels of IL-12, IFN-gamma, and TLR9.ConclusionLocalized application of CpG-ODN on its own or in combination with SEB may potentially reduce the expression of the proinflammatory cytokine IL-5 in nonasthmatic patients and may be further developed as an immunotherapeutic agent.

Details

ISSN :
19458924
Volume :
23
Issue :
2
Database :
OpenAIRE
Journal :
American journal of rhinologyallergy
Accession number :
edsair.doi.dedup.....08dd27bcdaaf9f81a18f7100db94c136