Proinflammatory Effect of Carbon-Based Nanomaterials: In Vitro Study on Stimulation of Inflammasome NLRP3 via Destabilisation of Lysosomes

Abstract

Carbon-based nanomaterials (C-BNM) have recently attracted an increased attention as the materials with potential applications in industry and medicine. Bioresistance and proinflammatory potential of C-BNM is the main obstacle for their medicinal application which was documented in vivo and in vitro. However, there are still limited data especially on graphene derivatives such as graphene platelets (GP). In this work, we compared multi-walled carbon nanotubes (MWCNT) and two different types of pristine GP in their potential to activate inflammasome NLRP3 (The nod-like receptor family pyrin domain containing 3) in vitro. Our study is focused on exposure of THP-1/THP1-null cells and peripheral blood monocytes to C-BNM as representative models of canonical and alternative pathways, respectively. Although all nanomaterials were extensively accumulated in the cytoplasm, increasing doses of all C-BNM did not lead to cell death. We observed direct activation of NLRP3 via destabilization of lysosomes and release of cathepsin B into cytoplasm only in the case of MWCNTs. Direct activation of NLRP3 by both GP was statistically insignificant but could be induced by synergic action with muramyl dipeptide (MDP), as a representative molecule of the family of pathogen-associated molecular patterns (PAMPs). This study demonstrates a possible proinflammatory potential of GP and MWCNT acting through NLRP3 activation.

In Vitro Assessment of the Genotoxic Potential of Pristine Graphene Platelets

“…Detailed physicochemical characterization and a full description of the preparation of stock suspensions of GP (250 µg/mL) were stated in our recent work [ 14 ]. The basic characterization is briefly summarized in Table 1 .…”

An update on the regulatory mechanisms of NLRP3 inflammasome activation

“… 143 , 144 Recent studies have shown that carbon-based nanomaterials, such as multiwalled carbon nanotubes, can activate the NLRP3 inflammasome through lysosomal destabilization and release of cathepsin B. 145 Nicotine also induces lysosomal membrane permeability in endothelial cells and triggers the lysosomal release of cathepsin B, thus enhancing NLRP3 inflammasome activation. 146 Recent studies have suggested a more generalized function of cathepsin B in the activation of the NLRP3 inflammasome through a direct interaction with NLRP3 at the ER upon stimulation with multiple types of NLRP3 activators, including ATP and nigericin, as well as particulate matter.…”

pH Sensitive Dextran Coated Fluorescent Nanodiamonds as a Biomarker for HeLa Cells Endocytic Pathway and Increased Cellular Uptake

“…Nanodiamonds have excellent biocompatibility in many different cell lines (in vitro) like HT-29 [ 5 ], macrophages, yeast cells [ 6 ], BHK-21 [ 7 ], MCF-7 [ 8 ]. Prabhakar et al showed no toxicity after incubating MDA-MB-231 (human breast adenocarcinoma) cells with FNDs for 120 h. While other carbon nanomaterials have been reported to cause proinflammatory responses [ 9 ] this is not the case for nanodiamonds [ 10 ].…”