Ellagic acid가 대식세포의 면역조절작용에 미치는 영향과 Toll-like receptor 4 관련 작용기전 연구
Study on the Immunomodulatory Effects of Ellagic Acid and their Mechanisms Related to Toll-like Receptor 4 in Macrophages
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본 연구는 EA에 의한 대식세포의 활성화를 매개로 한 항암효과와 항암작용과 관련된 대식세포의 면역조절효과를 확인하였다. 연구 결과 EA에 의해 RAW264.7세포 및 peritoneal macrophage 모두에서 항암효과가 증가하였으며, 증가된대식세포의 항암효과는 TLR4 signaling을 blocking하는CLI-095을 함께 처리하였을 때 일부 감소되었다. 이는EA에 의한 항암 효과가 부분적으로 TLR4를 경유하는 기전으로 나타나는 것을 의미한다. 또한, EA에 대한 대식세포의 NO 분비조절효과를 측정하였으며, EA는 대식세포의NO 생성을 증가시켰으나, 인위적으로 염증을 유발시켜 NO 를 과도하게 분비한 상태에서는 NO 분비를 오히려 억제시키는 결과를 나타내었다. 이와 같이 EA에 의한 NO조절에대한 이중 효과는 인체에 면역증강과 항염증 효과라는 긍정적인 효과를 나타내는 방향으로 조절하고 있으므로 EA 를 이용한 항암요법의 보조제 및 면역보조제로써의 활용에유익할 것으로 사료된다. 향후 EA에 대한 항암 작용 및NO 조절에서 세포내 신호전달 작용기전에 대한 심도 있는연구가 진행되어야 할 것으로 보인다.
Abstract
Ellagic acid (EA) is a phenolic compound in fruits and nuts including raspberries, strawberries, grapes and walnuts. Previous studies have indicated that EA possesses antioxidant activity, growth-inhibition and apoptosis-promoting activity in cancer cells. However, macrophage mediated cytotoxicity and immunomodulating effects on cancer cells have not been clarified. In the present study, we show that EA increased effects on macrophage mediated tumoricidal activity and NO production without direct tumor cell cytotoxicity. To further determine whether TLR4 (toll like receptor 4) is involved in anti-tumor activity, cells were treated TLR4 signaling inhibitor, CLI-095 in the presence of EA. CLI-095 treatment partially reduced macrophage-mediated tumoridial activity. EA also has inhibitory effects of NO production induced by LPS, whereas phagocytic activity was not changed. These results suggest that EA induces macrophage mediated tumoricidal activity which is partially related to TLR4 signaling and has a potential adjuvant in cancer therapy.
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