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


METHODS
An 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 SEB for 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 deltaC(T)) method used to determine interleukin (IL)-5, p35 IL-12, interferon (IFN) gamma, and TLR9 expression levels.


RESULTS
CpG-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.


CONCLUSIONS
Localized 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.
Tan
Lorwai
L
Department of Surgery-Otorhinolaryngology Head and Neck Surgery, University of Adelaide, The Queen Elizabeth Hospital, Adelaide, Australia.
Rogers
Trisha J
TJ
Hatzirodos
Nick
N
Baker
Leonie M
LM
Ooi
Enghooi
E
Wormald
Peter-John
PJ
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001249:Asthma / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D015331:Cohort Studies; D004768:Enterotoxins / Q000276:immunology / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007155:Immunologic Factors / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D015848:Interleukin-5 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009298:Nasal Polyps; D009838:Oligodeoxyribonucleotides / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D010256:Paranasal Sinuses / Q000473:pathology; D020545:Respiratory Mucosa / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D012220:Rhinitis / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D012852:Sinusitis / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D013211:Staphylococcus aureus; D046509:Tissue Culture Techniques; D051217:Toll-Like Receptor 9 / Q000235:genetics
C513533:CpG ODN 2006; D004768:Enterotoxins; D007155:Immunologic Factors; D015848:Interleukin-5; D009838:Oligodeoxyribonucleotides; C495371:TLR9 protein, human; D051217:Toll-Like Receptor 9; C031818:enterotoxin B, staphylococcal