單層奈米碳管於肺部上皮細胞中藉由影響Annexin A1與NF-κB間蛋白質交互作用減弱發炎訊號

Abstract

Single-walled carbon nanotubes (SWCNTs), one of the most popular used nanomaterials, have been developed as potential biomaterials or drug carriers. However, these nanomaterials may have some adverse effects or toxicities, which may be partly caused by interaction with some cellular proteins, but the mechanism is still unclear. Here, the SWCNTs-binding proteins or if SWCNTs can interact with certain protein complex were discovered in lung epithelial cells. By the electrophoresis and liquid chromatography-mass spectrometry (LCMS/MS), the ex-vivo result showed that Annexin A1 (ANXA1) is one of the potential candidates of SWCNTs-binding proteins. Since ANXA1 has been reported involving in inflammatory signaling and plays an important role in the activation of NF-κB signaling through protein-protein interaction. Our results demonstrated that the protein complex of ANXA1 and NF-κB could be interrupted by short form of SWCNTs (0.7 to 3 μm) both in vitro and ex-vivo. Importantly, TNF-α induced nucleus translocation of NF-κB and up-regulation of IL-8 expression were significantly decreased via treatment with SWCNTs (10 μg/ml) in human lung epithelial cells (A549 and Beas2b cells). According to our results, ANXA1 is a novel binding protein of SWCNTs. Through binding with ANXA1, SWCNTs can inhibit TNF-α induced NF-κB inflammatory cascade via interfering the protein complex of ANXA1/NF-κB in lung epithelial cells. This study provides the potential evidence and mechanisms to show how the SWCNTs can regulate immuno-response in pulmonary epithelial cells.