Kashem Mohammad Abul, Ren Xiaoou, Li Hongzhao, Liang Binhua, Li Lin, Lin Francis, Plummer Francis A, Luo Ma
Department of Medical Microbiology and Infectious Diseases, University of Manitoba, Winnipeg, MB, Canada.
JC Wilt Infectious Diseases Research Centre, Winnipeg, MB, Canada.
Front Cell Dev Biol. 2020 Jul 3;8:563. doi: 10.3389/fcell.2020.00563. eCollection 2020.
TILRR has been identified as an important modulator of inflammatory responses. It is associated with NF-κB activation, and inflammation. Our previous study showed that TILRR significantly increased the expression of many innate immune responsive genes and increased the production of several pro-inflammatory cytokines/chemokines by cervical epithelial cells. In this study, we evaluated the effect of TILRR-induced pro-inflammatory cytokines/chemokines on the migration of immune cells. The effect of culture supernatants of TILRR-overexpressed cervical epithelial cells on the migration of THP-1 monocytes and MOLT-4 T-lymphocytes was evaluated using Transwell assay and a novel microfluidic device. We showed that the culture supernatants of TILRR-overexpressed HeLa cells attracted significantly more THP-1 cells (11-40%, = 0.0004-0.0373) and MOLT-4 cells (14-17%, = 0.0010-0.0225) than that of controls. The microfluidic device-recorded image analysis showed that significantly higher amount with longer mean cell migration distance of THP-1 ( < 0.0001-0.0180) and MOLT-4 ( < 0.0001-0.0025) cells was observed toward the supernatants of TILRR-overexpressed cervical epithelial cells compared to that of the controls. Thus, the cytokines/chemokines secreted by the TILRR-overexpressed cervical epithelial cells attracted immune cells, such as monocytes and T cells, and may potentially influence immune cell infiltration in tissues.
TILRR已被确定为炎症反应的重要调节因子。它与核因子κB激活及炎症相关。我们之前的研究表明,TILRR可显著增加许多固有免疫反应基因的表达,并增加宫颈上皮细胞分泌多种促炎细胞因子/趋化因子。在本研究中,我们评估了TILRR诱导的促炎细胞因子/趋化因子对免疫细胞迁移的影响。使用Transwell试验和一种新型微流控装置评估了过表达TILRR的宫颈上皮细胞培养上清液对THP-1单核细胞和MOLT-4 T淋巴细胞迁移的影响。我们发现,过表达TILRR的HeLa细胞培养上清液吸引的THP-1细胞(11 - 40%,P = 0.0004 - 0.0373)和MOLT-4细胞(14 - 17%,P = 0.0010 - 0.0225)明显多于对照组。微流控装置记录的图像分析显示,与对照组相比,在过表达TILRR的宫颈上皮细胞培养上清液作用下,观察到THP-1细胞(P < 0.0001 - 0.0180)和MOLT-4细胞(P < 0.0001 - 0.0025)的迁移数量显著更多,平均细胞迁移距离更长。因此,过表达TILRR的宫颈上皮细胞分泌的细胞因子/趋化因子可吸引免疫细胞,如单核细胞和T细胞,并可能潜在影响组织中的免疫细胞浸润。