Abstract
Toxicology studies on pristine graphene are limited and lack significant correlations with actual human response. The goal of the current study was to determine the response of total colonic human tissue to pristine graphene exposure. Biopsy punches of colon tissues from healthy human were used to assess the biological response after ex vivo exposure to graphene at three different concentrations (1, 10, and 100 µg/mL). mRNA expression of specific genes or intestinal cytokine abundance was assessed using real-time PCR or multiplex immunoassays, respectively. Pristine graphene-activated genes that are related to binding and adhesion (GTPase and KRAS) within 2 h of exposure. Furthermore, the PCNA (proliferating cell nuclear antigen) gene was upregulated after exposure to graphene at all concentrations. Ingenuity pathway analysis revealed that STAT3 and VEGF signaling pathways (known to be involved in cell proliferation and growth) were upregulated. Graphene exposure (10 µg/mL) for 24 h significantly increased levels of pro-inflammatory cytokines IFNγ, IL-8, IL-17, IL-6, IL-9, MIP-1α, and Eotaxin. Collectively, these results indicated that graphene may activate the STAT3–IL23–IL17 response axis. The findings in this study provide information on toxicity evaluation using a human-relevant ex vivo colon model and serve as a basis for further exploration of its bio-applications.
Highlights
With the rise of nanotechnology in the last decade, many nanomaterials have shown potential uses in real applications
Colon tissue exposed to graphene at 10 μg/mL is a good example of how four biofunctions showed early (2 h) and lasting activation (24 h) of different biofunctions (Figure 3B)
Data generated by real-time PCR were further analyzed by Ingenuity Pathway Analysis (IPA; v8.0, Qiagen, Valencia, CA, USA) software to identify the pathways and functions that were significantly affected due to graphene exposure The IPA software analyzed the real-time gene expression data based on algorithm predictions, providing a list of potential up regulators organized based on their z-scores
Summary
With the rise of nanotechnology in the last decade, many nanomaterials have shown potential uses in real applications. Recent research by our group has shown that carbon nanoparticles penetrate the cell membrane and change the gene expression profile of exposed T-84 epithelial cells [15]. The current study investigated the impact of graphene exposure through molecular profile (mRNA expression), as well as through levels of key cytokines/chemokines in the colonic tissue, to reveal the mechanisms by which graphene could interact with the human intestinal tract. Fresh human colon tissues from different subjects were exposed to pristine graphene to identify mRNA gene expression and immune responses. The activation of genes in response to pristine graphene exposure was triggered by the nanoparticle’s characteristics of the material rather than being a carbon allotrope Activated carbon, another carbon allotrope but not in a nano size, was used as a negative control and has shown a different gene expression response in comparison to pristine graphene (Figure 2). Real-time PCR data were further investigated with IPA to understand the pathways impacted by graphene exposure
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