Characterization of ENM Dynamic Dose-Dependent MOA in Lung with Respect to Immune Cells Infiltration

Show full item record



Permalink

http://hdl.handle.net/10138/346226

Citation

Serra , A , del Giudice , G , Kinaret , P A S , Saarimäki , L A , Poulsen , S S , Fortino , V , Halappanavar , S , Vogel , U & Greco , D 2022 , ' Characterization of ENM Dynamic Dose-Dependent MOA in Lung with Respect to Immune Cells Infiltration ' , Nanomaterials , vol. 12 , no. 12 , 2031 . https://doi.org/10.3390/nano12122031

Title: Characterization of ENM Dynamic Dose-Dependent MOA in Lung with Respect to Immune Cells Infiltration
Author: Serra, Angela; del Giudice, Giusy; Kinaret, Pia Anneli Sofia; Saarimäki, Laura Aliisa; Poulsen, Sarah Sos; Fortino, Vittorio; Halappanavar, Sabina; Vogel, Ulla; Greco, Dario
Contributor organization: Institute of Biotechnology
Date: 2022-06
Language: eng
Number of pages: 16
Belongs to series: Nanomaterials
ISSN: 2079-4991
DOI: https://doi.org/10.3390/nano12122031
URI: http://hdl.handle.net/10138/346226
Abstract: The molecular effects of exposures to engineered nanomaterials (ENMs) are still largely unknown. In classical inhalation toxicology, cell composition of bronchoalveolar lavage (BAL) is a toxicity indicator at the lung tissue level that can aid in interpreting pulmonary histological changes. Toxicogenomic approaches help characterize the mechanism of action (MOA) of ENMs by investigating the differentially expressed genes (DEG). However, dissecting which molecular mechanisms and events are directly induced by the exposure is not straightforward. It is now generally accepted that direct effects follow a monotonic dose-dependent pattern. Here, we applied an integrated modeling approach to study the MOA of four ENMs by retrieving the DEGs that also show a dynamic dose-dependent profile (dddtMOA). We further combined the information of the dddtMOA with the dose dependency of four immune cell populations derived from BAL counts. The dddtMOA analysis highlighted the specific adaptation pattern to each ENM. Furthermore, it revealed the distinct effect of the ENM physicochemical properties on the induced immune response. Finally, we report three genes dose-dependent in all the exposures and correlated with immune deregulation in the lung. The characterization of dddtMOA for ENM exposures, both for apical endpoints and molecular responses, can further promote toxicogenomic approaches in a regulatory context.
Subject: engineered nanomaterials
toxicogenomics
dose-dependent
TinderMIX
bronchoalveolar lavage
multiwalled carbon nanotubes
titanium dioxide
carbon black
mechanism of action
biomarker
TITANIUM-DIOXIDE NANOPARTICLES
GENE-EXPRESSION CHANGES
NF-KAPPA-B
CARBON NANOTUBES
INFLAMMATORY RESPONSES
PULMONARY INFLAMMATION
EXPOSURE
NANOMATERIALS
ASPIRATION
ACTIVATION
1182 Biochemistry, cell and molecular biology
Peer reviewed: Yes
Rights: cc_by
Usage restriction: openAccess
Self-archived version: publishedVersion


Files in this item

Total number of downloads: Loading...

Files Size Format View
nanomaterials_12_02031.pdf 7.231Mb PDF View/Open

This item appears in the following Collection(s)

Show full item record