PTEN down-regulates IL-17 expression in a murine model of toluene diisocyanate-induced airway disease

Ri Kim So, Sun Lee Kyung, Ju Park Seoung, Kyung-Hoon Min, Young Lee Ka, Hun Yeong, Rae Lee Young, Suk Kim Jong, Jong Hong Soo, Chul Lee Yong

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Abstract

Toluene diisocyanate (TDI)-induced airway disease is a disorder characterized by chronic airway inflammation and airway remodeling. A recently discovered group of cytokines is the IL-17 family, which has been introduced as an important regulator of immune and inflammatory responses, including airway inflammation. Recently, we have reported that phosphatase and tensin homologue deleted on chromosome 10 (PTEN) plays a pivotal role in the pathogenesis of bronchial asthma. However, there are no available data for the effects of PTEN or IL-17 on TDI-induced airway disease and the relationship between PTEN and IL-17. We used a murine model to determine the role of PTEN in the pathogenesis of TDI-induced airway disease and the regulation of IL-17 production. These mice developed the typical pathophysiological features of TDI-induced airway disease and increased IL-17 expression in the lungs. Administration of phosphoinositide 3-kinase inhibitors or adenoviruses carrying PTEN cDNA (AdPTEN) reduced the pathophysiological features of TDI-induced airway disease and decreased the increased levels of IL-17 expression. Our results also showed that PI3K inhibitors or AdPTEN down-regulated a transcription factor, NF-κB activity, and BAY 11-7085 substantially reduced the increased levels of IL-17 after TDI inhalation. We also found that inhibition of IL-17 activity with an anti-IL-17 Ab reduced airway inflammation and airway hyperresponsiveness. These results suggest that PTEN plays a protective role in the pathogenesis of TDI-induced airway disease, at least in part through the regulation of IL-17 expression. Thus, PTEN may be a useful target for treating TDI-induced airway disease by modulating IL-17 expression.

Original languageEnglish
Pages (from-to)6820-6829
Number of pages10
JournalJournal of Immunology
Volume179
Issue number10
Publication statusPublished - 2007 Nov 15
Externally publishedYes

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ASJC Scopus subject areas

  • Immunology

Cite this

So, R. K., Kyung, S. L., Seoung, J. P., Min, K-H., Ka, Y. L., Yeong, H., Young, R. L., Jong, S. K., Soo, J. H., & Yong, C. L. (2007). PTEN down-regulates IL-17 expression in a murine model of toluene diisocyanate-induced airway disease. Journal of Immunology, 179(10), 6820-6829.