Department of Infection Biology, Zoonosis Research Center, Wonkwang University School of Medicine, Iksan, Jeonbuk, 570-749, South Korea.
Mol Cell Biochem. 2013 Feb;374(1-2):29-36. doi: 10.1007/s11010-012-1502-9. Epub 2012 Nov 9.
ACTG-toxin H (AH) originates from Alternaria sp. In this study, we explored the molecular mechanism underlying the anti-inflammatory properties of AH. Treatment with AH inhibited lipopolysaccharide (LPS)-induced interleukin-6, IL-1β, inducible nitric oxide synthase, and cyclooxygenase-2 expression and nitric oxide production. Furthermore, AH inhibited LPS-induced P38 MAPK and Akt activation in RAW264.7 cells. Electrophoretic mobility shift assays (EMSAs) showed that AH inhibited LPS-induced nuclear factor-κB (NFκB) DNA-binding activity. Using transfection assay and measurement of an NFκB-sensitive promoter region, we found that transfection of toll-like receptor 4 (TLR4) increased LPS-induced NFκB transcription activity in 293T cells. AH significantly blocked LPS-induced NFκB activation in TLR4-transfected cells. Taken together, our data indicated that anti-inflammatory properties of AH resulted from the inhibition of proinflammatory cytokines and enzyme production via the TLR4/NFκB signaling pathway.
ACTG-毒素 H（AH）来源于交链孢霉属。在本研究中，我们探讨了 AH 抗炎特性的分子机制。AH 处理抑制脂多糖（LPS）诱导的白细胞介素-6、IL-1β、诱导型一氧化氮合酶和环氧化酶-2 的表达和一氧化氮的产生。此外，AH 抑制 LPS 诱导的 RAW264.7 细胞中 P38 MAPK 和 Akt 的激活。电泳迁移率变动分析（EMSA）显示，AH 抑制 LPS 诱导的核因子-κB（NFκB）DNA 结合活性。通过转染实验和 NFκB 敏感启动子区域的测量，我们发现 TLR4 的转染增加了 293T 细胞中 LPS 诱导的 NFκB 转录活性。AH 显著阻断了 TLR4 转染细胞中 LPS 诱导的 NFκB 激活。总之，我们的数据表明，AH 的抗炎特性是通过 TLR4/NFκB 信号通路抑制促炎细胞因子和酶的产生而产生的。
