莫斯卡汀抑制脂多糖诱导的 RAW264.7 细胞中 HIF-1α的积累和 NF-κB 的激活。

Moscatilin repressed lipopolysaccharide-induced HIF-1alpha accumulation and NF-kappaB activation in murine RAW264.7 cells.

机构信息

Pharmacological Institute, College of Medicine, National Taiwan University, Taipei, Taiwan.

出版信息

Shock. 2010 Jan;33(1):70-5. doi: 10.1097/SHK.0b013e3181a7ff4a.

PMID:19487987

Abstract

In the present study, we investigated the signaling pathways involved in the inhibition of cyclooxygenase 2 (COX-2) and iNOS by moscatilin under LPS challenge in murine macrophage-derived cell line RAW264.7. The results showed that moscatilin (10-100 microM) had a significant inhibition in a concentration-dependent manner on proinflammatory enzymes (COX-2 and iNOS) expression and macrophage activation under LPS (100 ng/mL) treatment. Hypoxia-inducible factor 1 (HIF-1)alpha was reported to initiate inflammation under cytokine stimulation or hypoxic conditions. In addition, the increase in transcriptional activity and translation process of HIF-1alpha under LPS stimulation resulted in HIF-1alpha accumulation. Moscatilin, a purified compound from Chinese herbs, had a dominant repression on HIF-1alpha expression via down regulating HIF-1alpha mRNA without inhibition of cell viability, translation machinery, or proteasome-mediated degradation of HIF-1alpha. Moreover, the results showed that moscatilin suppressed nuclear translocation of nuclear factor (NF)-kappaB subunits, p65 and p50, and NF-kappaB activity by inhibiting phosphorylation of inhibitor of kappaBalpha. Taken together, we demonstrated that moscatilin inhibited both COX-2 and iNOS expressions after LPS treatment in RAW264.7. Furthermore, the inhibition of moscatilin seemed to be dependent on the repression of HIF-1alpha accumulation and NF-kappaB activation.

摘要

在本研究中，我们研究了在 LPS 刺激下，毛蕊花糖苷抑制环氧化酶 2 (COX-2) 和诱导型一氧化氮合酶 (iNOS) 的信号通路，该通路存在于小鼠巨噬细胞系 RAW264.7 中。结果表明，毛蕊花糖苷（10-100 μM）以浓度依赖性方式显著抑制 LPS（100ng/mL）处理后促炎酶（COX-2 和 iNOS）表达和巨噬细胞激活。缺氧诱导因子 1 (HIF-1)alpha 被报道在细胞因子刺激或缺氧条件下引发炎症。此外，LPS 刺激下 HIF-1alpha 转录活性和翻译过程的增加导致 HIF-1alpha 积累。毛蕊花糖苷是一种从中药中分离出来的纯化化合物，通过下调 HIF-1alpha mRNA 而不抑制细胞活力、翻译机制或蛋白酶体介导的 HIF-1alpha 降解，对 HIF-1alpha 表达具有明显的抑制作用。此外，结果表明，毛蕊花糖苷通过抑制 IκBα的磷酸化来抑制核因子 (NF)-κB 亚基 p65 和 p50 的核转位和 NF-κB 活性。总之，我们证明了毛蕊花糖苷在 LPS 处理后抑制了 RAW264.7 中的 COX-2 和 iNOS 表达。此外，毛蕊花糖苷的抑制作用似乎依赖于 HIF-1alpha 积累和 NF-κB 激活的抑制。