Chen F, Lu Y, Demers L M, Rojanasakul Y, Shi X, Vallyathan V, Castranova V
Department of Pathology, Pennsylvania State University College of Medicine, Milton S. Hershey Medical Center, Hershey, PA 17033, USA.
Ann Clin Lab Sci. 1998 Jan-Feb;28(1):1-13.
Nuclear transcription factor kappa B (NF-kappa B) is a multiprotein complex that regulates a variety of genes important for immunity and inflammation. The present study investigates the silica-induced activation of this transcription factor in mouse macrophage cell line RAW 264.7 cells, the role of free radical reactions in the mechanism of the activation, and its possible inhibition. Tetrandrine, a benzylisoquinoline alkaloid, which has been used as an antifibrotic drug to treat the lesions of silicosis and has been characterized as a hydroxyl radical (.OH) scavenger, inhibited the NF-kappa B activation induced by silica, lipopolysaccharide (LPS), and phorbol 12-myristate 13-acetate (PMA). Catalase, metal chelator, deferoxamine, and the silanol group (SiOH) blocker, poly(2-vinylpyridine-N-oxide) (PVPNO), also inhibited silica-induced NF-kappa B activation. Electron spin resonance (ESR) spin trapping measurements show that both deferoxamine and PVPNO decreased silica-mediated .OH radical generation from H2O2. It is shown that Fe(II) and not Fe(III) is able to cause NF-kappa B activation. The antioxidant, ascorbate, attenuated the NF-kappa B activation induced by silica but not by LPS. The .OH radical scavenger, sodium formate, inhibited NF-kappa B activation induced by silica but had only a minor effect on NF-kappa B activation induced by LPS. The results indicate that silica-mediated free radical generation via the Fenton or Fenton-like reaction (M(n)+ + H2O2-->M(n + 1)+ + OH- + .OH) and silanol groups on the silica surface play an important role in silica-induced NF-kappa B activation.
核转录因子κB（NF-κB）是一种多蛋白复合物，可调节多种对免疫和炎症至关重要的基因。本研究调查了二氧化硅在小鼠巨噬细胞系RAW 264.7细胞中诱导的该转录因子的激活、自由基反应在激活机制中的作用及其可能的抑制作用。粉防己碱是一种苄基异喹啉生物碱，已被用作抗纤维化药物来治疗矽肺病变，并且已被表征为羟基自由基（·OH）清除剂，它抑制了由二氧化硅、脂多糖（LPS）和佛波酯12-肉豆蔻酸酯13-乙酸酯（PMA）诱导的NF-κB激活。过氧化氢酶、金属螯合剂去铁胺以及硅醇基团（SiOH）阻断剂聚（2-乙烯基吡啶-N-氧化物）（PVPNO）也抑制了二氧化硅诱导的NF-κB激活。电子自旋共振（ESR）自旋捕获测量表明，去铁胺和PVPNO都减少了二氧化硅介导的H2O2产生的·OH自由基。结果表明，能够引起NF-κB激活的是Fe(II)而非Fe(III)。抗氧化剂抗坏血酸减弱了由二氧化硅诱导而非由LPS诱导的NF-κB激活。·OH自由基清除剂甲酸钠抑制了由二氧化硅诱导的NF-κB激活，但对由LPS诱导的NF-κB激活仅有轻微影响。结果表明，二氧化硅通过芬顿或类芬顿反应（M(n)+ + H2O2→M(n + 1)+ + OH- + ·OH）介导的自由基产生以及二氧化硅表面的硅醇基团在二氧化硅诱导的NF-κB激活中起重要作用。
