Conversion of Th17-type into Th2-type inflammation by acetyl salicylic acid via the adenosine and uric acid pathway in the lung

H. G. Moon, Y. M. Tae, Y. S. Kim, S. Gyu Jeon, S. Y. Oh, Y. Song Gho, Z. Zhu, Y. K. Kim

Research output: Contribution to journalArticle

Abstract

Background: Allergen-specific T-cell responses orchestrate airway inflammation, which is a characteristic of asthma. Recent evidence suggests that noneosinophilic asthma can be developed by mixed Th1 and Th17 cell responses when exposed to lipopolysaccharide (LPS)-containing allergens. Objective: To evaluate the therapeutic or adverse effects of acetyl salicylic acid (ASA) on the expression of Th1-type and Th17-type inflammation induced by airway exposure to LPS-containing allergens. Methods: Th1 + Th17 asthma and Th2 asthma mouse models were generated by intranasal sensitization with ovalbumin (OVA) and LPS and intraperitoneal sensitization with OVA and alum, respectively. Therapeutic or adverse effects were evaluated after allergen challenge using pharmacologic and transgenic approaches. Results: Lung infiltration of eosinophils was enhanced in OVA/LPS-sensitized mice by ASA treatment, which was accompanied by the enhanced production of eotaxin. These changes were associated with the down-regulation of Th17 cell response, which was partly dependent on adenosine receptor A1 and A3 subtypes, but up-regulation of allergen-specific IL-13 production from T cells. Lung inflammation induced by LPS-containing allergen was markedly reduced in IL-13-deficient mice in the context of ASA treatment, but not without ASA. Meanwhile, adenosine levels in the lung were enhanced by ASA treatment. Moreover, lung infiltration of eosinophils induced by ASA treatment was reversed by co-treatment of a xanthine oxidase inhibitor (allopurinol). Conclusion: These findings suggest that ASA changes Th17-type into Th2-type inflammation mainly via the adenosine and uric acid metabolic pathway in the lung.

Original languageEnglish (US)
Pages (from-to)1093-1103
Number of pages11
JournalAllergy: European Journal of Allergy and Clinical Immunology
Volume65
Issue number9
DOIs
StatePublished - Sep 1 2010

Keywords

  • Th17
  • Th2
  • acetyl salicylic acid
  • adenosine
  • asthma

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Fingerprint Dive into the research topics of 'Conversion of Th17-type into Th2-type inflammation by acetyl salicylic acid via the adenosine and uric acid pathway in the lung'. Together they form a unique fingerprint.

  • Cite this