사람 비만세포주에서 Clozapine과 Fluoxetine에 의한 케모카인 및 케모카인 수용체의 상이한 발현
Differential Effects of Clozapine and Fluoxetine on Expression of Chemokines and Chemokine Receptors in Human Mast Cell Line HMC-1
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목 적： 정신질환 병인에 면역계와의 관련성이 제시되고 있으며, clozapine 및 fluoxetine은 여러 cytokine들의 발현에 영향을 미친다고 한다. 최근 화학적 주성에 관련된 chemokine은 염증뿐만 아니라 중추신경계 질환의 병인에도 관련될 가능성을 보고하고 있다. Chemokine에는 CXC와 C chemokine 등이 있으며, 수 용체로는 CXCR1, 2, 3, 4와 CR1, 2, 3, 4 등이 알려져 있다. 본 연구는 clozapine과 fluoxetine에 의한 여러 chemo-kine과 그 수용체의 발현 양상을 알아보고자 하였다. 방 법： 사람 비만세포주(HMC-1)에 phorbol myristate ac -etate(PMA, 100ng/ml)와 calcium ionophore A23187 (350ng/ml)로 3시간 자극하여 chemokine과 그 수용체를 발현하게 하였다. Clozapine과 fluoxetine은 각 최종 농도 10-7 M로 1시간 전처치 하여 총 RNA를 추출하고 여러 chemokine과 수용체를 RT-PCR하였다.
Abstract
Objectives : It has been suggested that the immune system has a role in the pathophysiology of neuropsychiatric diseases. There are some reports that clozapine and fluoxetine affect on cytokine networks. Recently, it has been known that chemokines have chemotactic effect, and modulate a number of biological responses including the process of inflammation and the maintenance of CNS homeostasis. In the present study, we investigated the effect of clozapine or fluoxetine on the expression of chemokines and their receptors. Methods : Human mast cells(HMC-1) was incubated with phorbol myristate acetate(PMA, 100 ng/ml) and calcium ionophore A23187(350 ng/ml) for 3 hours. Clozapine(10-7M) or fluoxetine(10-7M) were pretreated for 1 hour. RT-PCR was performed for the detection of expression of various chemokines and chemokine receptors. Result : After treatment of clozapine, the expression of MCP-1, MIP-1β, CCR3, CXCR2, CXCR3 and CXCR4 were lower than the PMA/Ca ionophore-treated group, while the expression of MIP-1α, RANTES and IL-8 were not changed. However, fluoxetine was not affected the changes of expression of various chemokines and chemokine receptors. Conclusion : This result indicates that clozapine may affect on the expression of chemokines and chemokine receptors. Therefore, this study could, in part, provide the important basic data on the explanation of side effects of clozapine, such as fever and pancreatitis.