title: PTEN down-regulates IL-17 expression in a murine model of toluene diisocyanate-induced airway disease.
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-kappaB 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.
authors.affiliation: Department of Internal Medicine, Chonbuk National University Medical School, Jeonju, South Korea.
authors.forename: So Ri
authors.initials: SR
authors.lastname: Kim
authors.forename: Kyung Sun
authors.initials: KS
authors.lastname: Lee
authors.forename: Seoung Ju
authors.initials: SJ
authors.lastname: Park
authors.forename: Kyung Hoon
authors.initials: KH
authors.lastname: Min
authors.forename: Ka Young
authors.initials: KY
authors.lastname: Lee
authors.forename: Yeong Hun
authors.initials: YH
authors.lastname: Choe
authors.forename: Young Rae
authors.initials: YR
authors.lastname: Lee
authors.forename: Jong Suk
authors.initials: JS
authors.lastname: Kim
authors.forename: Soo Jong
authors.initials: SJ
authors.lastname: Hong
authors.forename: Yong Chul
authors.initials: YC
authors.lastname: Lee
mesh_terms: D000256:Adenoviridae; D000818:Animals; D001249:Asthma / Q000139:chemically induced / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects* / Q000235:genetics / Q000276:immunology; D005260:Female; D007249:Inflammation / Q000139:chemically induced / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D019570:Inhalation Exposure / Q000009:adverse effects; D020381:Interleukin-17 / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D009570:Nitriles / Q000494:pharmacology; D051059:PTEN Phosphohydrolase / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D013450:Sulfones / Q000494:pharmacology; D014051:Toluene 2,4-Diisocyanate / Q000633:toxicity*
chemical_list: D020381:Interleukin-17; D016328:NF-kappa B; D009570:Nitriles; D051059:PTEN Phosphohydrolase; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D013450:Sulfones; D014051:Toluene 2,4-Diisocyanate; C416282:BAY 11-7085; C487757:Pten protein, mouse