Abstract
Toxic effects of certain carbon nanomaterials (CNM) have been observed in several exposure scenarios both in vivo and in vitro. However, most of the data currently available has been generated in a high-dose/acute exposure setup, limiting the understanding of their immunomodulatory mechanisms. Here, macrophage-like THP-1 cells, exposed to ten different CNM for 48 h in low-cytotoxic concentration of 10 µg mL-1 , are characterized by secretion of different cytokines and global transcriptional changes. Subsequently, the relationships between cytokine secretion and transcriptional patterns are modeled, highlighting specific pathways related to alternative macrophage activation. Finally, time- and dose-dependent activation of transcription and secretion of M1 marker genes IL-1β and tumor necrosis factor, and M2 marker genes IL-10 and CSF1 is confirmed among the three most responsive CNM, with concentrations of 5, 10, and 20 µg mL-1 at 24, 48, and 72 h of exposure. These results underline CNM effects on the formation of cell microenvironment and gene expression leading to specific patterns of macrophage polarization. Taken together, these findings imply that, instead of a high and toxic CNM dose, a sub-lethal dose in controlled exposure setup can be utilized to alter the cell microenvironment and program antigen presenting cells, with fascinating implications for novel therapeutic strategies.
Highlights
Toxic effects of certain carbon nanomaterials (CNM) have been observed in effects are usually screened with relatively high doses, enabling evaluation of several exposure scenarios both in vivo and in vitro
The concentration of 10 μg mL−1 used in this study is suitable to investigate fine immunomodulatory effects of CNM, for it does not significantly impact on the cell viability and metabolism (Figure S3 in Scala et al.[19])
IL-1α, Interleukin 1β (IL-1β), IL-4, IL-5, IL-6, Interleukin 10 (IL-10), IL-17, IFNγ, and tumor necrosis factor (TNF) were quantified in the cell culture supernatant after 48-h exposure
Summary
Toxic effects of certain carbon nanomaterials (CNM) have been observed in effects are usually screened with relatively high doses, enabling evaluation of several exposure scenarios both in vivo and in vitro. Time- and dose-dependent activation of transcription and secretion of M1 marker genes IL-1β and tumor necrosis factor, and M2 marker genes IL-10 and CSF1 is confirmed among the three most responsive CNM, help to recruit other immune cells. They stimulate antigen-presenting cells (APC) to facilitate T-cell activation and adaptive immunity. Macrophages are extremely plastic cells, able to switch their phenotype after certain stimuli.[6,7] After with concentrations of 5, 10, and 20 μg mL−1 at 24, 48, and 72 h of exposure These results underline CNM effects on the formation of cell microenvironment and gene expression leading to specific patterns of macrophage polarization. Introduction macrophages as central mediators of immune system is well recognized and has been extensively characterized, nanoma-
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