TY - JOUR
T1 - Transcriptomic analysis revealed that multi-walled carbon nanotubes diameter-dependently induced pyroptosis in THP-1 macrophages
AU - Wang, Shuyi
AU - Ma, Jing
AU - Guo, Shuai
AU - Huang, Yuanyu
AU - Cao, Yi
N1 - Publisher Copyright:
© 2020 Elsevier B.V.
PY - 2020/10
Y1 - 2020/10
N2 - Direct contact with multi-walled carbon nanotubes (MWCNTs) could compromise the viability of macrophages, but the mechanisms remained poorly understood. Previously we investigated the cytotoxicity of MWCNTs with different diameters (XFM4 < XFM22 < XFM34), and showed that MWCNTs induced cytotoxicity in an order of XFM4 > XFM22 > XFM34. In this study, we analyzed the transcriptomic data and found that MWCNTs diameter-dependently (in an order of XFM4 > XFM22 > XFM34) affected gene ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways related with immune responses. Therefore, we speculated that MWCNT-induced cytotoxicity was inflammation-driving pyroptosis. To test this hypothesis, we investigated the changes of morphologies, reactive oxygen species (ROS) and key proteins related with pyroptosis. We found that only XFM4 induced multi-pores of cellular membranes and ROS. Meanwhile, MWCNTs promoted the protein levels of caspase 1, NLRP3, interleukin-18 (IL-18) and IL-1β, and the observed effects were typically more obvious for XFM4 compared with XFM22 or XFM34. Finally, we found that transfection with casp1 or nlrp3 siRNA down-regulated both pro-caspase 1 and NLRP3 proteins and consequently inhibited the cytotoxicity of XFM4. In conclusion, the results from this study suggested that MWCNTs induced pyroptosis in THP-1 macrophages. XFM4 more effectively promoted pyroptosis compared with XFM22 or XFM34, which could provide a basis for rational design of biocompatible MWCNTs.
AB - Direct contact with multi-walled carbon nanotubes (MWCNTs) could compromise the viability of macrophages, but the mechanisms remained poorly understood. Previously we investigated the cytotoxicity of MWCNTs with different diameters (XFM4 < XFM22 < XFM34), and showed that MWCNTs induced cytotoxicity in an order of XFM4 > XFM22 > XFM34. In this study, we analyzed the transcriptomic data and found that MWCNTs diameter-dependently (in an order of XFM4 > XFM22 > XFM34) affected gene ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways related with immune responses. Therefore, we speculated that MWCNT-induced cytotoxicity was inflammation-driving pyroptosis. To test this hypothesis, we investigated the changes of morphologies, reactive oxygen species (ROS) and key proteins related with pyroptosis. We found that only XFM4 induced multi-pores of cellular membranes and ROS. Meanwhile, MWCNTs promoted the protein levels of caspase 1, NLRP3, interleukin-18 (IL-18) and IL-1β, and the observed effects were typically more obvious for XFM4 compared with XFM22 or XFM34. Finally, we found that transfection with casp1 or nlrp3 siRNA down-regulated both pro-caspase 1 and NLRP3 proteins and consequently inhibited the cytotoxicity of XFM4. In conclusion, the results from this study suggested that MWCNTs induced pyroptosis in THP-1 macrophages. XFM4 more effectively promoted pyroptosis compared with XFM22 or XFM34, which could provide a basis for rational design of biocompatible MWCNTs.
KW - Multi-walled carbon nanotubes (MWCNTs)
KW - Pyroptosis
KW - RNAi
KW - THP-1 macrophages
KW - Transcriptomics
UR - http://www.scopus.com/inward/record.url?scp=85096244528&partnerID=8YFLogxK
U2 - 10.1016/j.impact.2020.100270
DO - 10.1016/j.impact.2020.100270
M3 - Article
AN - SCOPUS:85096244528
SN - 2452-0748
VL - 20
JO - NanoImpact
JF - NanoImpact
M1 - 100270
ER -
