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High aspect ratio nanomaterial-induced macrophage polarization is mediated by changes in miRNA levels
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SYSNO ASEP 0571226 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title High aspect ratio nanomaterial-induced macrophage polarization is mediated by changes in miRNA levels Author(s) Erdem, J. S. (NO)
Závodná, Táňa (UEM-P)
Ervik, T. K. (NO)
Skare, O. (NO)
Hron, Tomáš (UMG-J)
Anmarkrud, K. H. (NO)
Kusnierczyk, A. (NO)
Catalan, J. (ES)
Ellingsen, D. G. (NO)
Topinka, Jan (UEM-P) RID, ORCID
Zienolddiny-Narui, S. (NO)Number of authors 11 Article number 1111123 Source Title Frontiers in Immunology. - : Frontiers Media - ISSN 1664-3224
Roč. 14, JAN (2023)Number of pages 17 s. Language eng - English Country CH - Switzerland Keywords macrophage ; polarization ; nanomaterials ; inflammation ; fibrosis ; epigenetic ; miRNA OECD category Immunology R&D Projects LM2015073 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) EF16_013/0001821 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) Method of publishing Open access Institutional support UEM-P - RVO:68378041 ; UMG-J - RVO:68378050 UT WOS 000933031600001 EID SCOPUS 85147749301 DOI 10.3389/fimmu.2023.1111123 Annotation IntroductionInhalation of nanomaterials may induce inflammation in the lung which if left unresolved can manifest in pulmonary fibrosis. In these processes, alveolar macrophages have an essential role and timely modulation of the macrophage phenotype is imperative in the onset and resolution of inflammatory responses. This study aimed to investigate, the immunomodulating properties of two industrially relevant high aspect ratio nanomaterials, namely nanocellulose and multiwalled carbon nanotubes (MWCNT), in an alveolar macrophage model. MethodsMH-S alveolar macrophages were exposed at air-liquid interface to cellulose nanocrystals (CNC), cellulose nanofibers (CNF) and two MWCNT (NM-400 and NM-401). Following exposure, changes in macrophage polarization markers and secretion of inflammatory cytokines were analyzed. Furthermore, the potential contribution of epigenetic regulation in nanomaterial-induced macrophage polarization was investigated by assessing changes in epigenetic regulatory enzymes, miRNAs, and rRNA modifications. ResultsOur data illustrate that the investigated nanomaterials trigger phenotypic changes in alveolar macrophages, where CNF exposure leads to enhanced M1 phenotype and MWCNT promotes M2 phenotype. Furthermore, MWCNT exposure induced more prominent epigenetic regulatory events with changes in the expression of histone modification and DNA methylation enzymes as well as in miRNA transcript levels. MWCNT-enhanced changes in the macrophage phenotype were correlated with prominent downregulation of the histone methyltransferases Kmt2a and Smyd5 and histone deacetylases Hdac4, Hdac9 and Sirt1 indicating that both histone methylation and acetylation events may be critical in the Th2 responses to MWCNT. Furthermore, MWCNT as well as CNF exposure led to altered miRNA levels, where miR-155-5p, miR-16-1-3p, miR-25-3p, and miR-27a-5p were significantly regulated by both materials. PANTHER pathway analysis of the identified miRNA targets showed that both materials affected growth factor (PDGF, EGF and FGF), Ras/MAPKs, CCKR, GnRH-R, integrin, and endothelin signaling pathways. These pathways are important in inflammation or in the activation, polarization, migration, and regulation of phagocytic capacity of macrophages. In addition, pathways involved in interleukin, WNT and TGFB signaling were highly enriched following MWCNT exposure. ConclusionTogether, these data support the importance of macrophage phenotypic changes in the onset and resolution of inflammation and identify epigenetic patterns in macrophages which may be critical in nanomaterial-induced inflammation and fibrosis. Workplace Institute of Molecular Genetics Contact Nikol Škňouřilová, nikol.sknourilova@img.cas.cz, Tel.: 241 063 217 Year of Publishing 2024 Electronic address https://www.frontiersin.org/articles/10.3389/fimmu.2023.1111123/full
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