Glutathione peroxidase 2 (GPx2) is one of the five selenoprotein GPxs having a selenocysteine in the active center. GPx2 is strongly expressed in the gastrointestinal epithelium, as is another isoform, GPx1, though with a different localization pattern. Both GPxs are redox-active enzymes that are important for the reduction of hydroperoxides.

Studies on GPx2-deficient mice and human HT-29 cells with a stable knockdown (kd) of GPx2 revealed higher basal and IL-1β-induced expression of NF-κB target genes in vivo and in vitro. The activation of the IKK–IκBα–NF-κB pathway was increased in cultured GPx2 kd cells. Basal signaling was only restored by re-expressing active GPx2 in GPx2 kd cells but not by redox-inactive GPx2. As it is still not clear if the two isoforms GPx1 and GPx2 have different functions, kd cell lines for either GPx1 or GPx2 were studied in parallel. The inhibitory effect of GPx2 on NF-κB signaling and its target gene expression was stronger than that of GPx1, whereas cyclooxygenase (COX)- and lipoxygenase (LOX)-derived lipid mediator levels increased more strongly in GPx1 kd than in GPx2 kd cells. Under unstimulated conditions, the levels of the COX-derived prostaglandins PGE₂ and PGD₂ were enhanced in GPx2 as well as in GPx1 kd compared to control cells. Specifically, in GPx1 kd cells IL-1β stimulation led to a dramatic shift of the PGE₂/PGD₂ ratio towards pro-inflammatory PGE₂.

Taken together, GPx2 and GPx1 have overlapping functions in controlling inflammatory lipid mediator synthesis and, most probably, exert their anti-inflammatory effects by preventing excessive PGE₂ production. In view of the high activity of COX and LOX pathways during inflammatory bowel disease our data therefore provide new insights into the mechanisms of the protective function of GPx1 and GPx2 during colitis as well as inflammation-driven carcinogenesis.

谷胱甘肽过氧化物酶2（GPx2）是在活动中心具有硒代半胱氨酸的5种硒蛋白GPx之一。GPx2与另一种同工型GPx1在胃肠道上皮中强烈表达，尽管具有不同的定位模式。两种GPx都是氧化还原活性酶，对减少氢过氧化物很重要。

对GPx2缺陷小鼠和具有稳定的GPx2敲低（kd）的人HT-29细胞的研究表明，在体内和体外，较高的基础和IL-1β诱导的NF-κB靶基因表达。在培养的GPx2 kd细胞中，IKK–IκBα–NF-κB途径的激活增加。仅通过在GPx2 kd细胞中重新表达活性GPx2才能恢复基础信号，而不能通过不使用氧化还原的GPx2来恢复基础信号。由于尚不清楚两个同工型GPx1和GPx2是否具有不同的功能，因此并行研究了GPx1或GPx2的kd细胞系。GPx2对NF-κB信号转导及其靶基因表达的抑制作用比GPx1强，而GPx1 kd产生的环氧化酶（COX）和脂氧合酶（LOX）衍生的脂质介体水平比GPx2 kd细胞更强。在不受刺激的条件下，COX衍生的前列腺素PGE ₂和PGD _2的水平与对照细胞相比，GPx2和GPx1 kd的蛋白表达均得到了增强。具体而言，在GPx1 kd细胞中，IL-1β刺激导致PGE ₂ / PGD ₂比朝着促炎性PGE ₂急剧转变。

两者合计，GPx2和GPx1在控制炎症脂质介体合成方面具有重叠的功能，并且很可能通过防止过量的PGE ₂产生发挥其抗炎作用。鉴于炎症性肠病期间COX和LOX途径的高活性，我们的数据因此提供了对结肠炎期间GPx1和GPx2的保护功能机制以及炎症驱动的致癌作用的新见解。