RT Journal Article
SR Electronic
T1 Overproduction of IL-18 in the lungs induces IL-13 and IFN-g producing CD4+ T cell in the lungs, and results in airway hyperresponsiveness in Balb/c mice
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP p3273
VO 38
IS Suppl 55
A1 Sawada, Masanori
A1 Hoshino, Tomoaki
A1 Sakazaki, Yuki
A1 Oda, Hanako
A1 Takenaka, Shinich
A1 Kinoshita, Takashi
A1 Imaoka, Haruki
A1 Kawayama, Tomotaka
A1 Aizawa, Hisamichi
YR 2011
UL http://erj.ersjournals.com/content/38/Suppl_55/p3273.abstract
AB We newly established Balb/c background IL-18 transgenic (TG) mice using the human surfactant protein C promoter to drive expression of mature mouse IL-18 cDNA in the lungs. After sensitization on days 0 and 5 with ovalbumin (OVA), mice were challenged with OVA aerosol on day 19. Pulmonary inflammations and airway hyperresponsiveness (AHR) were examined on day 20. We previously reported that constitutive mouse mature IL-18 overproduction in the lungs of C57BL/6 mice induces emphysema (Am J Respir Crit Care Med 2007, 176:49-62). In contrast to C57BL/6 IL-18 TG mice, emphysematous changes were not observed in the lungs of Balb/c IL-18 TG mice. AHR to inhaled acetylcholine were not induced in non-treated Balb/c IL-18 TG mice. However, AHR and airway inflammation accompanied with CD4+ T cells, eosinophils and neutrophils were significantly and greatly increased in OVA-sensitized/challenged Balb/c IL-18 TG mice, when compared with OVA-sensitized/challenged WT Balb/c mice. Moreover, levels of IFN-g and IL-13 in the bronchoalveolar lavage fluid of OVA-sensitized/challenged Balb/c IL-18 TG mice were significantly elevated when compared with OVA-sensitized/challenged WT Balb/c mice. We used anti-CD4 mab or Balb/c IL-18 TG/IL-13 KO mice to examine the role of CD4+ T cells and IL-13 in this Balb/c IL-18 TG mouse. Anti-CD4 mab decrease the level of IL-13 and IFN-g. AHR and pulmonary inflammations were decreased in anti-CD4 mab or Balb/c IL-18 TG/IL-13 KO mice. This study suggested that overproducing IL-18 proteins in the lungs of Balb/c mice induce IL-13 and CD4+ T cells which may involve in the pathogenesis of asthma.