Journal of Clinical Immunology

, Volume 30, Issue 3, pp 459–464 | Cite as

Toll-like Receptor Expression on Peripheral Blood Mononuclear Cells in Asthmatics; Implications for Asthma Management

  • Eunyoung Chun
  • So-Hee Lee
  • Soo-Yeon Lee
  • Eun-Jin Shim
  • Sang-Heon Cho
  • Kyung-Up Min
  • You-Young Kim
  • Heung-Woo Park
Article

Abstract

Background

Accumulating evidence indicates that cells expressing Toll-like receptors (TLRs) play an important role in allergic diseases. The authors undertook this study to explore the hypothesis that TLR-mediated inflammatory signals are important from the perspective of asthma management.

Methods

The expressions of TLR1, TLR2, TLR3, TLR4, TLR6, and TLR9 and levels of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6, IL-8, and IFN-γ) on the peripheral blood mononuclear cells (PBMCs) of 36 stable asthmatics on treatment (the on-treatment group), 15 asthmatics (the treatment-naïve group) before and after a 7-day course of oral prednisolone (30 mg/day), and on the PBMCs of 15 healthy controls were measured after in vitro stimulation using TLR-specific ligands.

Results

In the on-treatment group, TLR1, TLR2, TLR6, and TLR9 expressions on PBMCs were significantly different between asthmatics and controls. And the expression of TLR4 on PBMCs and TNF-α production stimulated by lipopolysaccharide (LPS), were significantly higher in mild to moderate than in severe asthmatics. Interestingly, in the treatment-naïve group, short-term prednisolone significantly increased LPS-induced TNF-α and IFN-γ productions by PBMCs.

Conclusion

TLR-mediated inflammatory signals contribute to the development and severity of asthma and are not reduced by glucocorticoid treatment, which suggests that a TLR-specific antagonist and glucocorticoid are required for the effective control of airway inflammation in asthmatics.

Keywords

Asthma glucocorticoids peripheral blood mononuclear cells toll-like receptors 

Abbreviations

LPS

Lipopolysaccharide

PAMPs

Pathogen-associated molecular patterns

PBMCs

Peripheral blood mononuclear cells

PGN

Peptidoglycan

TLRs

Toll-like receptors

Supplementary material

10875_2009_9363_MOESM1_ESM.doc (61 kb)
ESM 1(DOC 61 kb)

References

  1. 1.
    Medzhitov R. Toll-like receptors and innate immunity. Nat Rev Immunol. 2001;1:135–45.CrossRefPubMedGoogle Scholar
  2. 2.
    Koch A, Knobloch J, Dammhayn C, et al. Effect of bacterial endotoxin LPS on expression of INF-gamma and IL-5 in T-lymphocytes from asthmatics. Clin Immunol. 2007;125:194–204.CrossRefPubMedGoogle Scholar
  3. 3.
    Sukkar MB, Xie S, Khorasani NM, et al. Toll-like receptor 2, 3, and 4 expression and function in human airway smooth muscle. J Allergy Clin Immunol. 2006;118:641–8.CrossRefPubMedGoogle Scholar
  4. 4.
    Lun SW, Wong CK, Ko FW, et al. Expression and functional analysis of toll-like receptors of peripheral blood cells in asthmatic patients: implication for immunopathological mechanism in asthma. J Clin Immunol. 2009;29:330–42.CrossRefPubMedGoogle Scholar
  5. 5.
    Woodruff PG, Khashayar R, Lazarus SC, et al. Relationship between airway inflammation, hyperresponsiveness, and obstruction in asthma. J Allergy Clin Immunol. 2001;108:753–8.CrossRefPubMedGoogle Scholar
  6. 6.
    Fahy JV. Eosinophilic and neutrophilic inflammation in asthma: insights from clinical studies. Proc Am Thorac Soc. 2009;6:256–9.CrossRefPubMedGoogle Scholar
  7. 7.
    Michel O. Role of lipopolysaccharide (LPS) in asthma and other pulmonary conditions. J Endotoxin Res. 2003;9:293–300.PubMedGoogle Scholar
  8. 8.
    National Institutes of Health. National Heart, Lung, and Blood Institute. 2007. National asthma education and prevention program expert panel report II: guidelines for the diagnosis and management of asthma. U.S. Department of Health and Human Services, Bethesda, MD. NIH Publication No. 08-4051Google Scholar
  9. 9.
    Boulet LP, Becker A, Bérubé D, et al. Canadian asthma consensus report. Can Med Assoc J. 1999;161(Suppl11):S1–62.Google Scholar
  10. 10.
    Ungar WJ, Champman KR, Santos MT. Assessment of a medication-based asthma index for population research. Am J Respir Crit Care Med. 2002;165:190–4.PubMedGoogle Scholar
  11. 11.
    Camateros P, Moisan J, Hénault J, et al. Toll-like receptors, cytokines and the immunotherapeutics of asthma. Curr Pharm Des. 2006;12:2365–74.CrossRefPubMedGoogle Scholar
  12. 12.
    Brightling C, Berry M, Amrani Y. Targeting TNF-alpha: a novel therapeutic approach for asthma. J Allergy Clin Immunol. 2008;121:5–10.CrossRefPubMedGoogle Scholar
  13. 13.
    Michel O. Role of lipopolysaccharide (LPS) in asthma and other pulmonary conditions. J Endotoxin Res. 2003;9:293–300.PubMedGoogle Scholar
  14. 14.
    Zhang N, Truong-Tran QA, Tancowny B, et al. Glucocorticoids enhance or spare innate immunity: effects in airway epithelium are mediated by CCAAT/enhancer binding proteins. J Immunol. 2007;179:578–89.PubMedGoogle Scholar
  15. 15.
    Schleimer RP. Glucocorticoids suppress inflammation but spare innate immune responses in airway epithelium. Proc Am Thorac Soc. 2004;1:222–30.CrossRefPubMedGoogle Scholar
  16. 16.
    Morjaria JB, Chauhan AJ, Babu KS, et al. The role of a soluble TNFα receptor fusion protein (etanercept) in corticosteroid refractory asthma: a double blind, randomised, placebo controlled trial. Thorax. 2008;63:584–91.CrossRefPubMedGoogle Scholar
  17. 17.
    Erin EM, Leaker BR, Nicholson GC, et al. The effects of a monoclonal antibody directed against tumor necrosis factor-α in asthma. Am J Respir Crit Care Med. 2006;174:753–62.CrossRefPubMedGoogle Scholar
  18. 18.
    Wenzel SE, Barnes PJ, Bleecker ER, et al. A randomized, double-blind, placebo-controlled study of tumor necrosis factor α blockade in severe persistent asthma. Am J Respir Crit Care Med. 2009;179:549–58.CrossRefPubMedGoogle Scholar
  19. 19.
    Yang M, Kumar RK, Foster PS. Interferon-gamma and pulmonary macrophages contribute to the mechanisms underlying prolonged airway hyperresponsiveness. Clin Exp Allergy. 2009;40:163–73.Google Scholar
  20. 20.
    Jeon SG, Oh SY, Park HK, et al. TH2 and TH1 lung inflammation induced by airway allergen sensitization with low and high doses of double-stranded RNA. J Allergy Clin Immunol. 2007;120:803–12.CrossRefPubMedGoogle Scholar
  21. 21.
    Kumar RK, Webb DC, Herbert C, et al. Interferon-gamma as a possible target in chronic asthma. Inflamm Allergy Drug Targets. 2006;5:253–6.CrossRefPubMedGoogle Scholar
  22. 22.
    Sin DD, Sutherland ER. Obesity and the lung: 4. Obesity and asthma. Thorax. 2008;63:1018–23.CrossRefPubMedGoogle Scholar
  23. 23.
    Babu KS, Salvi SS. Aspirin and asthma. Chest. 2000;118:1470–6.CrossRefPubMedGoogle Scholar
  24. 24.
    Nahm DH, Lee KH, Shin JY, et al. Identification of alpha-enolase as an autoantigen associated with severe asthma. J Allergy Clin Immunol. 2006;118:376–81.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Eunyoung Chun
    • 1
    • 2
  • So-Hee Lee
    • 1
    • 2
  • Soo-Yeon Lee
    • 1
    • 2
  • Eun-Jin Shim
    • 1
    • 2
  • Sang-Heon Cho
    • 1
    • 2
  • Kyung-Up Min
    • 1
    • 2
  • You-Young Kim
    • 1
    • 2
  • Heung-Woo Park
    • 1
    • 2
  1. 1.Department of Internal MedicineSeoul National UniversitySeoulRepublic of Korea
  2. 2.Institute of Allergy and Clinical ImmunologySeoul National University College of MedicineSeoulRepublic of Korea

Personalised recommendations