Department of Medical and Pharmaceutical Biotechnology, IMC University of Applied Sciences, 3500 Krems, Austria.
Department for Biomedical Research, University for Continuing Education Krems, 3500 Krems, Austria.
Cells. 2023 May 19;12(10):1425. doi: 10.3390/cells12101425.
The interaction between monocytes and endothelial cells in inflammation is central to chemoattraction, adhesion, and transendothelial migration. Key players, such as selectins and their ligands, integrins, and other adhesion molecules, and their functions in these processes are well studied. Toll-like receptor 2 (TLR2), expressed in monocytes, is critical for sensing invading pathogens and initiating a rapid and effective immune response. However, the extended role of TLR2 in monocyte adhesion and migration has only been partially elucidated. To address this question, we performed several functional cell-based assays using monocyte-like wild type (WT), TLR2 knock-out (KO), and TLR2 knock-in (KI) THP-1 cells. We found that TLR2 promotes the faster and stronger adhesion of monocytes to the endothelium and a more intense endothelial barrier disruption after endothelial activation. In addition, we performed quantitative mass spectrometry, STRING protein analysis, and RT-qPCR, which not only revealed the association of TLR2 with specific integrins but also uncovered novel proteins affected by TLR2. In conclusion, we show that unstimulated TLR2 influences cell adhesion, endothelial barrier disruption, migration, and actin polymerization.
单核细胞与内皮细胞在炎症中的相互作用是趋化、黏附和跨内皮迁移的核心。选择素及其配体、整合素和其他黏附分子等关键分子及其在这些过程中的功能已得到深入研究。单核细胞中表达的 Toll 样受体 2（TLR2）对于感知入侵病原体和启动快速有效的免疫反应至关重要。然而，TLR2 在单核细胞黏附和迁移中的扩展作用仅部分阐明。为了解决这个问题，我们使用单核细胞样野生型（WT）、TLR2 敲除（KO）和 TLR2 敲入（KI）THP-1 细胞进行了几项基于细胞的功能测定。我们发现 TLR2 促进单核细胞更快、更强地黏附到内皮细胞上，并在内皮细胞激活后导致更强的内皮屏障破坏。此外，我们进行了定量质谱分析、STRING 蛋白分析和 RT-qPCR，不仅揭示了 TLR2 与特定整合素的关联，还发现了受 TLR2 影响的新蛋白。总之，我们表明未受刺激的 TLR2 会影响细胞黏附、内皮屏障破坏、迁移和肌动蛋白聚合。
