Project description:Multi-walled carbon nanotubes (MWCNTs) are among the most promising nanomaterials because of their physical and chemical properties. However, since they are biopersistent fiber-like materials which share similarities with asbestos, concerns have arisen about their health effects. With their various industrial usages, occupational exposure to MWCNTs may occur mainly by inhalation as these nanomaterials can get aerosolised. The number of toxicological studies on CNTs has steadily increased for the last decades. Different works showed that MWCNT exposure by inhalation or intratracheal instillation could lead to pulmonary toxicity, such as lung inflammation, genotoxicity, fibrosis or lung cancer (Kasai et al. 2015, Kasai et al. 2016, Porter et al. 2013, Suzui et al. 2016). To date, only one MWCNT (MWNT-7) has been classified as possibly carcinogen to human (Group 2B) while the others have not been as classifiable as to their carcinogenicity to humans (Group 3) because of the lack of data on their carcinogenic potential (IARC 2017). Because of the wide variety of CNTs with various length, diameter or functionalisation, additional effort is required to assess their pulmonary toxicity. As a complementary approach to conventional toxicological assays, the omics methods are useful technologies for the mechanistic understanding of the toxicological effects observed following exposure to chemicals and particulate matters. Importantly, they can also be used as predictive tools for identifying the mode of action of other particles with similar physical and chemical characteristics. These molecular approaches may also be used for the discovery of exposure markers or early markers of adverse effects, before the appearance of clinical signs of a disease (Rahman et al. 2017). Several studies assessed gene expression alteration following in vivo exposure to CNTs (Poulsen et al. 2015, Snyder-Talkington et al. 2013, Ellinger-Ziegelbauer and Pauluhn 2009). These omics approaches were used to identify genes and pathways modulated in response to exposure. However, there are still too few studies to assess the link between MWCNT physico-chemical properties, global gene or protein expression profiles, and long-term effects. In a previous study, we showed that inhalation of two pristine MWCNTs, the long and thick NM-401, and the short and thin NM-403, induced alveolar neutrophilic granulocyte influx, a hallmark of inflammation, which was proportional to the lung CNT BET surface deposited dose (Gate et al. 2019). However, due to their different physical and chemical properties, one could assume that these two CNTs may have diverse toxicological profiles, but the conventional toxicology approaches used in this early work were probably not sensitive enough to identify such differences. In order to gain additional insight about their toxicological properties, in the current study, we compare the alteration induced by the two MWCNTs on the transcriptome in the lung tissue and the proteome in the broncho-alveolar lavage fluid (BALF) after rat exposure by inhalation. The omics analyses were performed from 3 days up to 180 days.

Project description:Animal and human studies suggest that inflammation is associated with behavioral disorders including aggression. We have recently shown that physical aggression of boys during childhood is strongly associated with reduced plasma levels of cytokines IL-1a, IL-4, IL-6, IL-8 and IL-10, later in early adulthood (Provencal et al., unpublished data). This study tests the hypothesis that there is an association between differential DNA methylation regions in cytokine genes in T cells and monocytes DNA in adult subjects and a trajectory of physical aggression from childhood to adolescence. We compared the methylation profiles of the entire genomic loci encompassing the IL-1a, IL-6, IL-4, IL10 and IL8 and three of their regulatory transcription factors (TF) NFkB1, NFAT5 and STAT6 genes in adult males on a chronic physical aggression trajectory (CPA) and males with the same background who followed a normal physical aggression trajectory (control group). We used the method of methylated DNA immunoprecipitation (MeDIP) with comprehensive cytokine gene loci and TF loci microarray hybridization, statistical analysis and false discovery rate correction. We recruited two groups of Caucasian males who were born in families with a low socioeconomic status and were living at the time of the present study within 200km from our laboratory. The first group, composed of 8 subjects, had a history of chronic physical aggression from age 6 to 15 years (chronic physical aggression group, CPA). The second group, composed of 12 subjects, was recruited from the same longitudinal studies but included only those who did not have a history of chronic physical aggression from age 6 to 15 (Control group, CG). Using custom-designed microarrays with 44K probes tiling cytokines IL-1a, IL-6, IL-4, IL10 and IL8 and three of their regulatory transcription factors (TF) NFkB1, NFAT5 and STAT6, we obtained DNA methylation profiles by meDIP-chip. Each profile was generated in triplicate.

Dataset Information

Differentially expressed genes between C.elegans with low physical ability and with high physical ability

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