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Articles by M. Orita
Total Records ( 2 ) for M. Orita
  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.
  T. Kurita , K. Nakamura , M. Tabuchi , M. Orita , K. Ooshima and H. Higashino
  The details of pharmacological mechanisms of Gorei-san, a traditional Japanese Kampo medicine, remains to be clarified, although it has been used for diuretic and hydrostatic purposes. From these circumstances, the effects of this medicine on the expressions of aquaporin (AQP) 1, 2, 3, 4 and vasopressin 2 receptor (V2R) mRNAs were investigated in relation to diuresis and water balance regulation in the kidney and brain. Gorei-san extract decocted with hot water was given to rats loaded with 50 mL kg-1 volume of physiological saline and AQP1, 2, 3, 4 and V2R mRNAs were measured with real-time polymerase chain reaction (PCR) in the cortex and the medulla of kidney and the forebrain. A low dose of Gorei-san extract (100 mg kg-1) led to an increase in urine excretion and lower AQP3 mRNA expression in the cortex as well as lower expression of AQP2 and AQP3 mRNAs in the medulla of kidney, whereas no change in V2R mRNA expression was observed. AQP1 mRNA expression decreased in the forebrain of rats loaded with an excess volume of physiological saline compared with rats not loaded with excess saline and given no agent. A low dose of Gorei-san extract increased urine excretion volume, probably due to the downregulation of AQP3 mRNA in the cortex and downregulation of AQP2 and AQP3 mRNAs in the medulla of the kidney, in which changes were not related to V2R mRNA expression. An excess volume of physiological saline given to rats caused an inhibition of AQP1 mRNA expression in the forebrain, which probably functioned to maintain the water balance in a hyper-hydrous state.
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