Respiratory Syncytial Virus에 감염된 인간 기도 상피세포에서 RANTES 생산에 미치는 코르티코스테로이드의 영향
Effects of Corticosteroids on RANTES Production in Human Bronchial Epithelial Cell with Respiratory Syncytial Virus Infection
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목 적:소아에서 respiratory syncytial virus (RSV) 감염은 천식을 악화시키는 중요한 인자들 중 하나이다. 사람에서 RSV는 일차적으로 기도 상피세포를 목표로 하고, 기도에서 염증반응을 유발하는 regulated on activation normal T-cell expressed and secreted(RANTES)같은 케모카인을 분비하여 염증반응을 나타난다. 흡입용 코르티코스테로이드를 포함한 여러 가지 코르티코스테로이드는 항염증작용으로 천식 악화의 예방에 매우 효과적인 약제이다. 본 연구에서는 RSV에 감염된 인간 기도 상피세포주의 RANTES 유전자 전사와 분비 조절에 있어서 다양한 코르티코스테로이드들의 효과가 어떻게 나타나는지 알아보고, 특히 기도 상피세포에서 RSV 감염 전과 후에 각각 처치한 코르티코스테로이드로 인해 RANTES 분비에 차이가 있는지 알아보았다. 방 법:인간 기도 상피세포인 BEAS-2B 세포에 RSV를 감염시키고 budesonide(BUD), fluticasone propionate(FP), methylprednisolone (MP)을 감염 전후에 각각 처리하여 RANTES 분비를 관찰하였다. 전처치 군에서는 BEAS-2B 세포에 FP, BUD, MP를 농도를 달리하여 24시간 동안 처리한 후 RSV를 감염시켰다. 후처치 군에서는 BEAS-2B에 RSV를 감염시킨 후 코르티코스테로이드의 농도를 달리하여 24시간 동안 처리하였다. 상층액에서 ELISA를 사용하여 RANTES 양을 측정하였다. 결 과:전처치군에서는 코르티코스테로이드의 억제정도에 통계학적으로 유의한 차이를 관찰할 수 없었다. 반면 후처치군에서는 BUD>FP= MP로 억제 능력 차이를 볼 수 있었다.(P<0.05) 전 후처치군의 비교에서는 BUD에서 후처치시 더 강한 억제 효과를 보였다.(P<0.05) 결 론:흡입용 코르티코스테로이드를 포함한 다양한 코르티코스테로이드들의 인간 기도 상피세포에서 RANTES 생산 억제 효과는 코르티코스테로이드의 종류와 적용 시기에 따라서 매우 다양하게 나타났다.
Abstract
Purpose:Respiratory syncytial virus(RSV) which is the most common cause of bronchiolitis in infants is an important triggering factor of asthma exacerbation in children. This virus stimulates chemokine such as regulated on activation normal T-cell expressed and secreted(RANTES) production by human airway epithelial cells in vitro. Corticosteroids are effective medications for prevention of asthma exacerbation. We examined whether the inhibitory effect of corticosteroid on RANTES production in human bronchial epithelial cells (BEAS-2B) infected with RSV varies according to the kinds of corticosteroids and the timing of corticosteroid treatment in vitro. Methods:In the pretreatment group, BEAS-2B cells were pretreated with budesonide (BUD), fluticasone propionate(FP), or methylprednisolone(MP), and then the cells were infected with RSV. The supernatants of the cell culture were collected after virus infection. In the posttreatment group, BEAS-2B cells were infected with RSV, and then treated with corticosteroid, and the supernatants of the cell culture were collected. RANTES levels in each of the collected supernatant were determined. Results:In the pretreatment group, the strength of each corticosteroid's inhibitory effect on RANTES product was not significantly different. In the posttreatment group, the strength of the inhibitory effect on the production of RANTES was in the order of BUD>MP=FP. BUD have more inhibitory effect on RANTES production at posttreatment group. Conclusion:The inhibitory effect of corticosteroid on the production of RANTES in BEAS-2B cells infected with RSV varied widely according to the kinds of corticosteroids and the timing of the corticosteroid treatment
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