Pariano Marilena, Costantini Claudio, Santarelli Ilaria, Puccetti Matteo, Giovagnoli Stefano, Talesa Vincenzo N, Romani Luigina, Antognelli Cinzia
Department of Medicine and Surgery, University of Perugia, 06132 Perugia, Italy.
Department of Pharmaceutical Science, University of Perugia, 06132 Perugia, Italy.
Vaccines (Basel). 2021 Nov 11;9(11):1311. doi: 10.3390/vaccines9111311.
Cystic fibrosis (CF) is an autosomal recessive disorder that affects multiple organs, although a decline in respiratory function represents the major cause of morbidity and mortality. The airways of CF patients are characterized by a chronic inflammatory state to which the receptor for advanced glycation end-products greatly contributes. Glyoxalase 1 (GLO1) is the major enzyme metabolizing methylglyoxal, a potent precursor of advanced glycation end-products. Its role in CF has never been investigated. We herein resorted to murine and human preclinical models of CF to define the contribution of GLO1 to inflammatory pathology. We found that the expression and activity of GLO1, measured by real-time PCR and Western blot or a specific spectrophotometric assay, respectively, are defective in mice and human bronchial cells from CF patients exposed to , a common pathogen in CF, but could be restored upon blockade of interleukin-1 receptor signaling by anakinra in mice. This study suggests that GLO1 contributes to pathology in CF and may be potentially targeted to mitigate inflammation.
囊性纤维化（CF）是一种常染色体隐性疾病，可影响多个器官，不过呼吸功能下降是发病和死亡的主要原因。CF患者的气道具有慢性炎症状态的特征，晚期糖基化终产物受体在其中起了很大作用。乙二醛酶1（GLO1）是代谢甲基乙二醛的主要酶，甲基乙二醛是晚期糖基化终产物的一种强效前体。其在CF中的作用从未被研究过。我们在此借助CF的小鼠和人类临床前模型来确定GLO1对炎症病理的作用。我们发现，分别通过实时PCR、蛋白质印迹法或特定分光光度法测定，在暴露于CF常见病原体的CF患者的小鼠和人支气管细胞中，GLO1的表达和活性存在缺陷，但在小鼠中通过阿那白滞素阻断白细胞介素-1受体信号传导后，其表达和活性可恢复。这项研究表明，GLO1在CF病理中起作用，并且可能是减轻炎症的潜在靶点。
