Akbaba Tayfun Hilmi, Akkaya-Ulum Yeliz Z, Demir Selcan, Ozen Seza, Balci-Peynircioglu Banu
Department of Medical Biology, Hacettepe University Faculty of Medicine, Ankara, Turkey.
Division of Rheumatology, Department of Pediatrics, Hacettepe University Faculty of Medicine, Ankara, Turkey.
Pediatr Res. 2022 May;91(6):1399-1404. doi: 10.1038/s41390-021-01559-7. Epub 2021 May 7.
Familial Mediterranean fever (FMF) is an autoinflammatory disease caused by pathogenic variants of the MEFV gene, which encodes pyrin. Leukocyte migration to serosal sites is a key event during inflammation in FMF. The pyrin inflammasome is a multiprotein complex involved in inflammation. Here, we aimed to determine the relationship between inflammatory cell migration and the pyrin inflammasome in FMF patients.
Monocytes were isolated from blood samples collected from patients with FMF, healthy controls, and a patient with cryopyrin-associated periodic syndrome (CAPS), which served as a disease control. Inflammasome proteins were analyzed under inflammasome activation and inhibition by western blotting. Cell migration assays were performed with the isolated primary monocytes as well as THP-1 monocytes and THP-1-derived macrophages.
When the pyrin inflammasome was suppressed, migration of monocytes from FMF patients was significantly decreased compared to the migration of monocytes from the CAPS patient and healthy controls. Cell line experiments showed a relationship between pyrin inflammasome activation and cell migration.
These findings suggest that the increased cell migration in FMF is due to the presence of more active pyrin inflammasome. This study contributes to our understanding of the role of pyrin in inflammatory cell migration through inflammasome formation.
The pyrin inflammasome may play a role in inflammatory cell migration. FMF patients show a pyrin inflammasome-dependent increase in inflammatory cell migration. Correlations between the pyrin inflammasome and cell migration were observed in both THP-1 monocytes and THP-1-derived macrophages.
家族性地中海热（FMF）是一种由编码吡啉的MEFV基因的致病变异引起的自身炎症性疾病。白细胞向浆膜部位的迁移是FMF炎症过程中的关键事件。吡啉炎性小体是一种参与炎症的多蛋白复合物。在此，我们旨在确定FMF患者炎症细胞迁移与吡啉炎性小体之间的关系。
从FMF患者、健康对照者以及一名作为疾病对照的冷吡啉相关周期性综合征（CAPS）患者采集的血液样本中分离单核细胞。通过蛋白质免疫印迹法在炎性小体激活和抑制条件下分析炎性小体蛋白。对分离出的原代单核细胞以及THP-1单核细胞和THP-1衍生的巨噬细胞进行细胞迁移试验。
当吡啉炎性小体受到抑制时，与CAPS患者和健康对照者的单核细胞迁移相比，FMF患者单核细胞的迁移显著减少。细胞系实验显示了吡啉炎性小体激活与细胞迁移之间的关系。
这些发现表明，FMF中细胞迁移增加是由于存在更活跃的吡啉炎性小体。本研究有助于我们理解吡啉通过炎性小体形成在炎症细胞迁移中的作用。
吡啉炎性小体可能在炎症细胞迁移中起作用。FMF患者炎症细胞迁移呈吡啉炎性小体依赖性增加。在THP-1单核细胞和THP-1衍生的巨噬细胞中均观察到吡啉炎性小体与细胞迁移之间的相关性。
