Marklund S L
Department of Clinical Chemistry, Umeå University Hospital, Sweden.
J Biol Chem. 1992 Apr 5;267(10):6696-701.
The influence of cytokines on extracellular superoxide dismutase (EC-SOD) expression by human dermal fibroblasts was investigated. The expression was markedly stimulated by interferon-gamma (IFN-gamma), was varying between fibroblast lines stimulated or depressed by interleukin-1 alpha (IL-1 alpha), was intermediately depressed by tumor necrosis factor-alpha (TNF-alpha), and markedly depressed by transforming growth factor-beta (TGF-beta). TNF-alpha, however, enhanced the stimulation by a high dose of IFN-gamma, whereas TGF-beta markedly depressed the stimulations given by IFN-gamma and IL-1 alpha. The ratio between the maximal stimulation and depression observed was around 30-fold. The responses were generally slow and developed over periods of several days. There were no effects of IFN-alpha, IL-2, IL-3, IL-4, IL-6, IL-8, granulocyte-macrophage colony-stimulating factor, human growth hormone, Escherichia coli lipopolysaccharide, leukotriene B4, prostaglandin E2, formylmethionylleucylphenylalanine, platelet-activating factor, and indomethacin. The cytokines influencing the EC-SOD expression are also known to influence superoxide production by leukocytes and other cell types, and the EC-SOD response pattern is roughly compatible with the notion that its function is to protect cells against extracellular superoxide radicals. The results show that EC-SOD is a participant in the complex inflammatory response orchestrated by cytokines. The CuZn-SOD activity of the fibroblasts was not influenced by any of the cytokines, whereas the Mn-SOD activity was depressed by TGF-beta. TNF-alpha, IL-1 alpha, and IFN-gamma stimulated the Mn-SOD activity, as previously known, and these responses were reduced by TGF-beta. The different responses of the three SOD isoenzymes illustrate their different physiological roles.
研究了细胞因子对人皮肤成纤维细胞胞外超氧化物歧化酶（EC-SOD）表达的影响。γ干扰素（IFN-γ）可显著刺激其表达，白细胞介素-1α（IL-1α）对不同成纤维细胞系的刺激或抑制作用有所不同，肿瘤坏死因子-α（TNF-α）可中度抑制其表达，而转化生长因子-β（TGF-β）则可显著抑制其表达。然而，TNF-α可增强高剂量IFN-γ的刺激作用，而TGF-β则可显著抑制IFN-γ和IL-1α的刺激作用。观察到的最大刺激与抑制之间的比值约为30倍。这些反应通常较为缓慢，且在数天内逐渐显现。α干扰素、IL-2、IL-3、IL-4、IL-6、IL-8、粒细胞-巨噬细胞集落刺激因子、人生长激素、大肠杆菌脂多糖、白三烯B4、前列腺素E2、甲酰甲硫氨酰亮氨酰苯丙氨酸、血小板活化因子和吲哚美辛均无影响。已知影响EC-SOD表达的细胞因子也会影响白细胞和其他细胞类型产生超氧化物，且EC-SOD的反应模式大致符合其功能是保护细胞免受细胞外超氧自由基侵害的观点。结果表明，EC-SOD参与了由细胞因子精心编排的复杂炎症反应。成纤维细胞的铜锌超氧化物歧化酶（CuZn-SOD）活性不受任何细胞因子的影响，而锰超氧化物歧化酶（Mn-SOD）活性则受到TGF-β的抑制。如先前所知，TNF-α、IL-1α和IFN-γ可刺激Mn-SOD活性，而这些反应会被TGF-β减弱。三种超氧化物歧化酶同工酶的不同反应说明了它们不同的生理作用。
