Chen Xi1, Jie Zhou2, Shuzhang Du3, Shaojun Peng4. 1. Pharmaceutical Department, The First Affiliated Hospital of Zhengzhou University, 450052, Zhengzhou, People's Republic of China. 2. School of Medicine, Yichun University, 576 XueFu Road, Yuanzhou District, 336000, Yichun, People's Republic of China. zj9032@126.com. 3. Pharmaceutical Department, The First Affiliated Hospital of Zhengzhou University, 450052, Zhengzhou, People's Republic of China. du_shuzhang@126.com. 4. School of Medicine, Yichun University, 576 XueFu Road, Yuanzhou District, 336000, Yichun, People's Republic of China.
Abstract
BACKGROUND: Our previous studies (Int J Nanomed 10:22, 2015) have indicated that a single large dose of mesoporous silica nanoparticles (MSNs) can induce severe and selective nephrotoxicity, which is closely related to inflammation mediated by the NF-κB pathway. However, the effect of MSNs on other organs and the interactions of nanomaterials with biological systems remain rudimentary. OBJECTIVE: This study aimed to clarify the biological behaviour and influence of MSNs on macrophages. METHODS: The mice received a single intraperitoneal injection of a suspension of 150, 300 of 600 mg/kg MSNs, and RAW 264.7 cells were treated with MSNs at various concentrations and times. Cell viability was determined by MTT assay and LDH release assay. The NF-κB pathway and the target proinflammatory cytokines IL-1β and TNF-α were determined by western blotting or ELISA. Autophagy is considered as an emerging mechanism of nanomaterials. So the autophagic ultrastructural analysis, the determination of Beclin-1 and LC3 expression, and the calculation of LC3II dots were employed to verify autophagy activation. In addition, RNA interference, autophagy agonist and inhibitor were used to explore the role of autophagy in inflammation. RESULTS: The results indicated that MSNs are internalized into macrophages and induce cytotoxicity in a dose- and time-dependent manner. The NF-κB pathway, IL-1β and TNF-α were induced and released by MSNs. The levels of Beclin-1 and LC3II dots were obviously up-regulated by MSNs, which indicated that autophagy was induced in the MSN-treated cells. Moreover, the enhanced autophagy can attenuate the inflammation mediated by the NF-κB pathway, whereas the inhibition of autophagy can contribute to inflammation. CONCLUSIONS: In summary, our results suggest that autophagy may be a possible protective factor in inflammation induced by MSNs in macrophages.
BACKGROUND: Our previous studies (Int J Nanomed 10:22, 2015) have indicated that a single large dose of mesoporous silica nanoparticles (MSNs) can induce severe and selective nephrotoxicity, which is closely related to inflammation mediated by the NF-κB pathway. However, the effect of MSNs on other organs and the interactions of nanomaterials with biological systems remain rudimentary. OBJECTIVE: This study aimed to clarify the biological behaviour and influence of MSNs on macrophages. METHODS: The mice received a single intraperitoneal injection of a suspension of 150, 300 of 600 mg/kg MSNs, and RAW 264.7 cells were treated with MSNs at various concentrations and times. Cell viability was determined by MTT assay and LDH release assay. The NF-κB pathway and the target proinflammatory cytokines IL-1β and TNF-α were determined by western blotting or ELISA. Autophagy is considered as an emerging mechanism of nanomaterials. So the autophagic ultrastructural analysis, the determination of Beclin-1 and LC3 expression, and the calculation of LC3II dots were employed to verify autophagy activation. In addition, RNA interference, autophagy agonist and inhibitor were used to explore the role of autophagy in inflammation. RESULTS: The results indicated that MSNs are internalized into macrophages and induce cytotoxicity in a dose- and time-dependent manner. The NF-κB pathway, IL-1β and TNF-α were induced and released by MSNs. The levels of Beclin-1 and LC3II dots were obviously up-regulated by MSNs, which indicated that autophagy was induced in the MSN-treated cells. Moreover, the enhanced autophagy can attenuate the inflammation mediated by the NF-κB pathway, whereas the inhibition of autophagy can contribute to inflammation. CONCLUSIONS: In summary, our results suggest that autophagy may be a possible protective factor in inflammation induced by MSNs in macrophages.
Authors: Ji Wang; Yang Li; Junchao Duan; Man Yang; Yang Yu; Lin Feng; Xiaozhe Yang; Xianqing Zhou; Zhendong Zhao; Zhiwei Sun Journal: Autophagy Date: 2018-07-20 Impact factor: 16.016
Authors: Massimiliano Bianchi; Martina Chiu; Giuseppe Taurino; Roberta Ruotolo; Nelson Marmiroli; Enrico Bergamaschi; Francesco Cubadda; Ovidio Bussolati Journal: Nanomaterials (Basel) Date: 2020-07-18 Impact factor: 5.076