In vitro anti-inflammatory and pro-aggregative effects of a lipid compound, petrocortyne A, from marine sponges
In vitro anti-inflammatory and pro-aggregative effects of a lipid compound, petrocortyne A, from marine sponges
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DOI：
10.1007/s00210-003-0848-7
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发表时间：
2003-12-01
影响因子：
3.6
通讯作者：
Cho, JY
中科院分区：
文献类型：
--
作者：
Hong, SY;Kim, SH;Cho, JY
(3S,14S)-Petrocortyne A 是一种来自海洋海绵 (Petrosia sp.) 的脂质化合物（C-46 聚乙炔醇），对多种实体瘤细胞具有有效的细胞毒性。在这项研究中，我们使用巨噬细胞和单核细胞系 RAW264.7 和 U937，研究了非细胞毒性浓度的石油可汀 A 对各种细胞炎症现象的体外抗炎和促聚集作用。 Petrocortyne A 在脂多糖 (LPS) 激活的 RAW264.7 细胞和佛波醇 12-肉豆蔻酸酯 13-乙酸酯 (PMA)/LPS 处理的 U937 细胞中以浓度依赖性方式强烈阻断肿瘤坏死因子-α (TNF-α) 的产生。它还阻断 LPS 或干扰素 (IFN) 处理的 RAW264.7 细胞中浓度依赖性的 NO 产生。在测试的迁移因子中，该化合物选择性阻断肝细胞生长因子/分散因子（HGF/SF）的表达。另一方面，通过细胞-细胞粘附测定评估，石油可丁A并没有阻断粘附分子聚集抗体诱导的粘附分子的活化，但显着抑制PMA诱导的细胞-细胞粘附。有趣的是，长期暴露（2 天和 3 天）后，石油可丁 A 诱导 U937 同型聚集，并伴有促聚集信号的微弱诱导，例如 p132 的酪氨酸磷酸化和细胞外信号相关激酶 1 和 2 (ERK 1/2) 的磷酸化。因此，Petrocortyne A 可能会抑制细胞炎症过程和免疫细胞向发炎组织的迁移。
(3S,14S)-Petrocortyne A, a lipid compound (a C-46 polyacetylenic alcohol), from marine sponges (Petrosia sp.) is potently cytotoxic against several solid tumour cells. In this study, we investigated in vitro anti-inflammatory and pro-aggregative effects of petrocortyne A at non-cytotoxic concentrations on various cellular inflammatory phenomena using the macrophage and monocytic cell lines RAW264.7 and U937. Petrocortyne A blocked tumour necrosis factor-alpha (TNF-alpha) production strongly and concentration-dependently in lipopolysaccharide (LPS)-activated RAW264.7 cells and phorbol 12-myristate 13-acetate (PMA)/LPS-treated U937 cells. It also blocked NO production concentration-dependently in LPS- or interferon (IFN)-gamma-treated RAW264.7 cells. Among the migration factors tested, the compound selectively blocked the expression of hepatocyte growth factor/scatter factor (HGF/SF). On the other hand, as assessed by a cell-cell adhesion assay, petrocortyne A did not block the activation of adhesion molecules induced by aggregative antibodies to adhesion molecules, but suppressed PMA-induced cell-cell adhesion significantly. Intriguingly, petrocortyne A induced U937 homotypic aggregation following long exposure (2 and 3 days), accompanied by weak induction of pro-aggregative signals such as tyrosine phosphorylation of p132 and phosphorylation of extracellular signal-related kinase 1 and 2 (ERK 1/2). Petrocortyne A may thus inhibit cellular inflammatory processes and immune cell migration to inflamed tissue.