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.
Highlights
Over the past decades, nanomaterials have attracted great attention with Carbon-based nanomaterials (C-BNM) being among the most studied ones
In our previous study we demonstrated the effect of 100 nm nanodiamonds on the injury of lysosomal membranes and the release of cathepsin B resulting in activation of inflammasome NLRP3 and release of IL-1β [6]
In our study using a well-established in vitro model, we have demonstrated a clear proinflammatory potential of graphene platelets (GP) and multi-walled carbon nanotubes (MWCNT) which can be enhanced by various pathogen-associated molecular patterns (PAMPs)
Summary
Nanomaterials have attracted great attention with C-BNM being among the most studied ones. It has been confirmed that GP, which are up to 25 μm in diameter, can be delivered beyond the ciliated airways and deposited in alveoli, where they can either persist in intercellular spaces, or are internalized by alveolar macrophages [29,30,31] This may lead to inflammation, disruption of homeostasis, and subsequent fibrosis and tissue damage [28,32,33,34]. Multi-layered graphene platelets induced a substantial inflammatory response and cytotoxicity in rat lungs [33]. Another pulmonary in vivo study which compared six different surface modifications of GP showed increased oxidative stress and acute inflammation [35]. A focus on deeper details on the mechanism of cytotoxicity and the inflammation of C-BNM is still necessary
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