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Articles by Y. Aragane
Total Records ( 2 ) for Y. Aragane
  Tz. Markova , M. Tabuchi , B. Alexieva , E. Nikolova , Y. Aragane and H. Higashino
  Phosphodiesterase (PDE) enzymes catalyze breakdown of cAMP and cGMP, which is known to have potent immunomodulatory capacity. Here, we aimed at clarifying whether PDE4 is involved in allergen-induced activation of immunocompetent cells. To address this issue, human peripheral blood-derived mononuclear cells (PBMC) were cultured with mite antigen, dermatophagoides farinae (Der-f), in the presence or the absence of a specific PDE4 inhibitor, rolipram or a non-selective PDE inhibitor theophylline. Semiquantitative RT-PCR analysis demonstrated that stimulation of cells with Der-f led to upregulated expression of IL-5 mRNA, which was clearly downregulated by both inhibitors. Downregulation of Der-f-induced IL5 mRNA was similarly observed when cells were treated with U0126, a specific MEK/ERK inhibitor. This suggests that ERK signaling pathways are involved in this event. This was further supported by the observation that rolipram as well as theophyllin interfered with phospholylation of ERK1/2 induced by Der-f as determined by Western blot analysis using an antibody directed against phospholylated ERK1/2. Finally, immunostaining showed that stimulation to PBMC with Der-f led to nuclear translocation of AP-1 components (JunD, Fra-2), whose migration was inhibited by rolipram, indicating the interference with activation of AP-1 transcription factors. Together, the present study indicates that allergen-induced activation of immunocompetent cells was prevented by rolipram through interference with ERK1/2 signaling.
  T.P. Markova , Y. Aragane , A. Niwa , M. Tabuchi , M. Orita , K. Ooshima and H. Higashino
  Phosphodiesterases (PDE) catalyze the breakdown of cAMP and thus, may have potent immunomodulatory activity. Theophyllin is a non-selective PDE inhibitor and has long been used to treat atopic diseases such as asthma, based on its well-known effects of the bronchodilative and anti-inflammatory effects, although the immune modulatory activities are not completely clear yet. Because it is believed that Th2-immnuity plays a pathogenic role in asthma, we were interested to study the mechanisms of how it modulates mite-allergen-induced activation of Th2-like immunity. To address this issue, peripheral blood mononuclear cells (PBMC) were prepared from human healthy volunteers, stimulated with mite-allergen dermatophagoides farinae (Der-f), RNA prepared and semi-quantitative RT-PCR was performed using primers specific for IL-5, a representative Th2 cytokine. Consequently, it was found that theophylline at a concentration of 10-6 to 10-5 M significantly downregulated Der-f-induced expression of IL-5 mRNA. Intriguingly, theophylline (10-5 M) inhibited the expression of IL-5 mRNA of PBMCs from patients allergic to house dust mite. To further explore the mechanisms involved, a PKA type I inhibitor Rp-8-Br-cAMPS was added, resulting in restoration of theophylline-downregulated expression of Der-f-induced IL-5 mRNA, indicating the involvement of PKA in this event. Together, the present study demonstrates that theophylline prevents allergen-induced PKA activation and thus may, at least in part, inhibit Th2-like immune responses.
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