Abstract
An increasing amount of products containing engineered nanoparticles is emerging. Among these particles are carbon nanotubes (CNTs) which are of interest for a wide range of industrial and biomedical applications. There have been raised concerns over the effects of CNTs on human health. Some types of CNTs are classified as group 2B carcinogens by the International Agency for Research on Cancer. CNTs may also induce pulmonary inflammatory and fibrotic effects. By utilizing CNTs of different lengths, we investigated the role of the proinflammatory cytokine, interleukin-1 (IL-1) on gap junctional intercellular communication (GJIC) by using IL-1 wild-type (IL1-WT) and IL-1 knock-out (IL1-KO) cells. GJIC decreased equally in both cell types after CNT exposure. Immunofluorescence staining showed Gja1 and Gjb2 in gap junctions and hemichannels for both cell types. Gjb1 and Gjb2 expression was low in IL1-KO cells, which was confirmed by protein analysis. Gja1 was upregulated with both CNTs, whereas Gjb1 was down-regulated by CNT-2 in IL1-WT cells. Connexin mRNA expression was regulated differently by the CNTs. CNT-1 affected Gja1 and Gjb2, whereas CNT-2 had an effect on Gjb1. CNTs negatively affect GJIC through gap junctions independently of the length of CNT and IL-1 status. Furthermore, connexin gene expression was affected by IL-1 at transcriptional and translational levels. As both CNTs used in this study are cytotoxic to the cells and reduce cell survival, we suggest that CNT-induced reduction in GJIC may be important for inhibiting transfer of cell survival signals between cells.Electronic supplementary materialThe online version of this article (doi:10.1007/s12079-016-0323-0) contains supplementary material, which is available to authorized users.
Highlights
There is increased focus on the potential negative health effects of exposure to manufactured carbon nanotubes (CNTs)
IL-1 wild-type (IL1-WT) and IL-1α/β double knock-out (IL1-KO) cells were exposed to 5 μg/ml of CNT-1 and CNT-2 for 24 h
Investigation of gap junctional intercellular communication (GJIC) showed that it was significantly higher in IL1-KO cells compared to IL1-WT cells both in the control and CNT exposed cells after 24 h
Summary
There is increased focus on the potential negative health effects of exposure to manufactured carbon nanotubes (CNTs). Inflammation and various signaling pathways may be important for communication between cells (Zhou and Jiang 2014). Intercellular communication is mediated by connexins which are proteins that form hemichannels and gap junction channels between cells. Whereas hemichannels are important for sampling of the extracellular milieu, the gap junction channels are necessary for direct intercellular communication. During the formation of an intercellular channel, six connexin proteins oligomerize into a hemichannel (connexon) and after docking to another hemichannel in an opposing cell the intact channel is formed. Gap junction channels mediate the diffusion of several small and hydrophilic substances including adenosine triphosphate, cyclic adenosine monophosphate, inositol triphosphate, glutathione, glutamate, glucose and several ions between cells (Alexander and Goldberg 2003). Intercellular communication through gap junctions is tightly controlled through rapid dynamic formation and degradation of the gap junctions in response to various types of stimuli including changes in voltage, pH or phosphorylation of connexins (Beardslee et al 1998, Herve et al 2007, Lampe and Lau 2004, Falk et al 2009, Gaietta et al 2002)
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