Tumurkhuu Gantsetseg, Koide Naoki, Dagvadorj Jargalsaikhan, Hassan Ferdaus, Islam Shamima, Naiki Yoshikazu, Mori Isamu, Yoshida Tomoaki, Yokochi Takashi
Department of Microbiology and Immunology, Aichi Medical University School of Medicine, Nagakute, Aichi, Japan.
FEMS Immunol Med Microbiol. 2007 Mar;49(2):304-11. doi: 10.1111/j.1574-695X.2006.00203.x. Epub 2007 Jan 10.
Antioxidants are able to inhibit inflammatory gene expression in response to lipopolysaccharide via down-regulating generation of intracellular reactive oxygen species (ROS) as second messengers. The effect of manganese (III) tetrakis (4-benzoic acid) porphyrin (MnTBAP), a synthetic metalloporphyrin with antioxidant activity, on tumor necrosis factor (TNF)-alpha production in lipopolysaccharide-stimulated RAW 264.7 macrophage cells was examined. MnTBAP prevented the generation of intracellular ROS in lipopolysaccharide-stimulated RAW 264.7 cells and further inhibited lipopolysaccharide-induced TNF-alpha production. MnTBAP exclusively prevented the phosphorylation of p38 mitogen-activated protein kinase (MAPK) and stress-activated protein kinase (SAPK/JNK) whereas it did not affect the phosphorylation and activation of nuclear factor-kappaB and extracellular signal regulated kinase 1/2. MnTBAP was suggested to inhibit lipopolysaccharide-induced TNF-alpha production by the prevention of intracellular ROS generation and subsequent inactivation of p38 MAPK and SAPK/JNK.
抗氧化剂能够通过下调作为第二信使的细胞内活性氧（ROS）的生成，来抑制对脂多糖产生反应的炎症基因表达。研究了具有抗氧化活性的合成金属卟啉四（4-苯甲酸）锰卟啉（MnTBAP）对脂多糖刺激的RAW 264.7巨噬细胞中肿瘤坏死因子（TNF）-α产生的影响。MnTBAP可防止脂多糖刺激的RAW 264.7细胞中细胞内ROS的生成，并进一步抑制脂多糖诱导的TNF-α产生。MnTBAP专门阻止p38丝裂原活化蛋白激酶（MAPK）和应激激活蛋白激酶（SAPK/JNK）的磷酸化，而不影响核因子-κB和细胞外信号调节激酶1/2的磷酸化和激活。研究表明，MnTBAP通过防止细胞内ROS的生成以及随后p38 MAPK和SAPK/JNK的失活，来抑制脂多糖诱导的TNF-α产生。
