Immunomodulatory activity of betulinic acid by producing pro-inflammatory cytokines and activation of macrophages
Immunomodulatory activity of betulinic acid by producing pro-inflammatory cytokines and activation of macrophages
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DOI：
10.1007/bf02994763
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发表时间：
2003-12-01
影响因子：
6.7
通讯作者：
Kim, KJ
中科院分区：
文献类型：
--
作者：
Yun, YH;Han, SH;Kim, KJ
白桦酸(BA)是从白桦树中分离得到的一种五环三萜类化合物，具有抗炎和免疫调节作用，是多种人类肿瘤细胞凋亡的选择性诱导剂。根据单核细胞和组织巨噬细胞在炎症和免疫反应中的关键作用，我们推测BA至少调节两类炎症蛋白介质，白介素1β(IL-1β)和肿瘤坏死因子-α(TNF-α)。BA在0.625和10µg/m L浓度下以剂量依赖方式产生肿瘤坏死因子-α和IL-1β。在2.5~20µg/mLBA浓度范围内，内毒素可抑制一氧化氮合酶相关NO的产生，而2.5~20µg/mLBA可抑制COX-2的表达。在内毒素刺激的RAW 264.7细胞和腹膜巨噬细胞中检测了这些炎症介质的调节作用。同时还观察了巨噬细胞的形态，当BA浓度为0.625时，巨噬细胞表面CD40分子表达增强，与加入或不加入内毒素的浓度相似。此外，BA(20µg/mL)通过产生DNA梯带促进RAW 264.7细胞的凋亡。结果表明，BA可诱导巨噬细胞和促炎细胞因子的激活。这可能为BA介导巨噬细胞、抑制炎症和调节免疫反应的能力提供了分子基础。
Betulinic acid (BA), a pentacyclic triterpene isolated from Lycopus lucidus, has been reported to be a selective inducer of apoptosis in various human cancer and shown anti-inflammatory and immunomodulatory properties. We postulated that BA modulates the immunomodulatory properties at least two groups of protein mediators of inflammation, interlukin-1beta (IL-1beta) and the tumor necrosis factor-alpha (TNF-alpha) on the basis of the critical role of the monocytes and tissue macrophages in inflammatory and immune responses. TNF-alpha and IL-1beta were produced by BA in a dose dependent manner at concentration of 0.625 and 10 mug/mL. The production of NO associated with NOS was inhibited when treated with LPS at the concentration of 2.5 to 20 mug/mL of BA whereas COX-2 expression was decreased at 2.5 to 20 mug/mL. These modulations of inflammatory mediators were examined in LPS-stimulated RAW 264.7 cells and peritoneal macrophages. The morphology of macrophage was also examined and enhanced surface CD 40 molecule was expressed when treated BA at 0.625similar to5 mug/mL with or without LPS. Furthermore, BA (20 mug/mL) enhanced apoptosis by producing DNA ladder in the RAW 264.7 cells. Our results indicated that BA induced activation of macrophage and pro-inflammatory cytokines. This may provide a molecular basis for the ability of BA to mediate macrophage, suppress inflammation, and modulate the immune response.