| Co-Investigator(Kenkyū-buntansha) |
ADACHI Tetsuo Gifu Pharmaceutical University, Professor, 薬学部, 教授 (40137063)
SAKUMA Masato Aichi Medical University, nephrology, Clin. Specialist, 医学部, 講師 (90257684)
FUTENMA Arao Aichi Medical University, nephrology, Clin. Specialist, 医学部, 助教授 (80173508)
宮井 宏暢 愛知医科大学, 医学部, 講師 (70190733)
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| Budget Amount *help |
¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2002: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 2001: ¥1,200,000 (Direct Cost: ¥1,200,000)
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| Research Abstract |
The kidney glomerular mesangial cells (MCs) are mesenchymally derived cell in a pivotal position to induce the oxygen radical injury through the cytokines production, which is the clinical target for glucocorticoid treatment in glomerular nephritis. In culture condition, MC shows exert several action including the oxygen radical and chemokine production by glucocorticoid or phorbol myristate acetate (PMA) stimulation. According to the modification of MC differentiation; experimental nephritis, immune-complex, EC-SOD production of MC, which is the important for reduction of oxygen radical toxity in extracellular space, was assessed through the cAMP and chemokine production. EC-SOD production of MC was recognized in early stage, and continues to stable in confluent state. The correlation of MC differentiation marker, oxygen radical production oxygenradical scavengers, EC-SOD production was positively correlated with MCs differentiation, negatively correlated with oxygen radical production. Among the ten cases, the glucocorticoid stimulation which induce the stable condition of MC, enhance the both of EC-SOD and cAMP production, suppress the IL-6 and IL-8 production in dose dependent manner. In contrast, PMA stimulation, which induce the activation of mesangial cell, enhance the both of the IL-6 and IL-8 production, suppress the EC-SOD and cAMP production. In unstimulat condition, EC-SOD production was positively correlated with cAMP content, negatively correlated with IL-6 and IL-8 production. The enhancement of the EC-SOD production in MC associate with the promotion of the cAMP production, result in the suppression of IL-6 and IL-8 production, may play the pathophisiological role of glomerular nephritis, suggest the one of the pharmacological activities in glucocorticoid.
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