Universität zu Köln

Mukherjee, Sourav P., Bondarenko, Olesja ORCID: 0000-0001-8767-1365, Kohonen, Pekka ORCID: 0000-0002-7845-3611, Andon, Fernando T., Brzicova, Tana, Gessner, Isabel ORCID: 0000-0001-9674-161X, Mathur, Sanjay, Bottini, Massimo ORCID: 0000-0001-9237-8972, Calligari, Paolo, Stella, Lorenzo ORCID: 0000-0002-5489-7381, Kisin, Elena, Shvedova, Anna, Autio, Reija ORCID: 0000-0002-6519-2715, Salminen-Mankonen, Heli, Lahesmaa, Riitta and Fadeel, Bengt (2018). Macrophage sensing of single-walled carbon nanotubes via Toll-like receptors. Sci Rep, 8. LONDON: NATURE PUBLISHING GROUP. ISSN 2045-2322

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Abstract

Carbon-based nanomaterials including carbon nanotubes (CNTs) have been shown to trigger inflammation. However, how these materials are 'sensed' by immune cells is not known. Here we compared the effects of two carbon-based nanomaterials, single-walled CNTs (SWCNTs) and graphene oxide (GO), on primary human monocyte-derived macrophages. Genome-wide transcriptomics assessment was performed at sub-cytotoxic doses. Pathway analysis of the microarray data revealed pronounced effects on chemokine-encoding genes in macrophages exposed to SWCNTs, but not in response to GO, and these results were validated by multiplex array-based cytokine and chemokine profiling. Conditioned medium from SWCNT-exposed cells acted as a chemoattractant for dendritic cells. Chemokine secretion was reduced upon inhibition of NF-kappa B, as predicted by upstream regulator analysis of the transcriptomics data, and Toll-like receptors (TLRs) and their adaptor molecule, MyD88 were shown to be important for CCL5 secretion. Moreover, a specific role for TLR2/4 was confirmed by using reporter cell lines. Computational studies to elucidate how SWCNTs may interact with TLR4 in the absence of a protein corona suggested that binding is guided mainly by hydrophobic interactions. Taken together, these results imply that CNTs may be 'sensed' as pathogens by immune cells.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Mukherjee, Sourav P. UNSPECIFIED UNSPECIFIED UNSPECIFIED Bondarenko, Olesja UNSPECIFIED orcid.org/0000-0001-8767-1365 UNSPECIFIED Kohonen, Pekka UNSPECIFIED orcid.org/0000-0002-7845-3611 UNSPECIFIED Andon, Fernando T. UNSPECIFIED UNSPECIFIED UNSPECIFIED Brzicova, Tana UNSPECIFIED UNSPECIFIED UNSPECIFIED Gessner, Isabel UNSPECIFIED orcid.org/0000-0001-9674-161X UNSPECIFIED Mathur, Sanjay UNSPECIFIED UNSPECIFIED UNSPECIFIED Bottini, Massimo UNSPECIFIED orcid.org/0000-0001-9237-8972 UNSPECIFIED Calligari, Paolo UNSPECIFIED UNSPECIFIED UNSPECIFIED Stella, Lorenzo UNSPECIFIED orcid.org/0000-0002-5489-7381 UNSPECIFIED Kisin, Elena UNSPECIFIED UNSPECIFIED UNSPECIFIED Shvedova, Anna UNSPECIFIED UNSPECIFIED UNSPECIFIED Autio, Reija UNSPECIFIED orcid.org/0000-0002-6519-2715 UNSPECIFIED Salminen-Mankonen, Heli UNSPECIFIED UNSPECIFIED UNSPECIFIED Lahesmaa, Riitta UNSPECIFIED UNSPECIFIED UNSPECIFIED Fadeel, Bengt UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-198717
DOI:	10.1038/s41598-018-19521-9
Journal or Publication Title:	Sci Rep
Volume:	8
Date:	2018
Publisher:	NATURE PUBLISHING GROUP
Place of Publication:	LONDON
ISSN:	2045-2322
Language:	English
Faculty:	Faculty of Mathematics and Natural Sciences
Divisions:	Faculty of Mathematics and Natural Sciences > Department of Chemistry > Institute of Inorganic Chemistry
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language PATTERN-RECOGNITION RECEPTORS; NF-KAPPA-B; GRAPHENE OXIDE; PROTEIN CORONA; IMMUNE-SYSTEM; INFLAMMATORY RESPONSES; DENDRITIC CELLS; ACTIVATION; TOXICITY; EXPRESSION Multiple languages Multidisciplinary Sciences Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/19871