Interestingly, this BTG regulated cell cycle pathway was also significant for cells
exposed to the highest concentration of TSC at the 6 h time point, with Btg1, Btg2 and Ccrn4l being up-regulated. In our earlier toxicogenomic analyses of three cigarette smoke condensates Btg2 was also found to be among the most up-regulated genes ( Yauk et al., 2011). Fig. 7 shows a comparison of the significantly http://www.selleckchem.com/products/AC-220.html altered cell cycle genes following exposure to the two smoke condensates. Although many of the same genes are affected and cell cycle appears to be a commonly disrupted function, there appears to be subtle differences in how this disruption occurs. Furthermore, cluster analyses of cell cycle genes (data not shown) confirms the importance of the smoke condensate type since cell cycle genes cluster primarily by smoke type, and subsequently by concentration. Both MSC and TSC exposed cells responded with Verteporfin supplier the up-regulation of inflammation related genes and pathways at the 6 h time point. These finding are consistent with the published literature, which notes that inflammation is typically seen in gene expression studies involving
tobacco smoke exposure (Bosio et al., 2002, Fields et al., 2005 and Lu et al., 2007). Similarly, mucosal biopsy, and bronchial lavage show that smoking marijuana is also consistently linked with airway inflammation (Lee and Hancox, 2011 and Roth et al., 1998). A gene expression study that examined human airway epithelial cells exposed to THC for 7 days showed an increase in Ptgs-2 and Il-1a levels, and it was hypothesized that the effect contributes to the airway inflammation observed in habitual marijuana smokers ( Sarafian et al., 2005). In the present study, it appeared that MSC might be a more potent inducer of the inflammatory Linifanib (ABT-869) response than TSC. At the highest concentration, 12 genes in the KEGG Cytokine-Cytokine Receptor Interaction Pathway were significantly
expressed following MSC exposure as opposed to 5 significantly expressed genes following TSC exposure. In addition, inflammatory related genes and IPA pathways (e.g., IL-10, IL-17, IL17A, IL-17F) were more significantly altered following MSC relative to TSC exposure (Supplementary Fig. 1). The Biosynthesis of Steroids Pathway was among the most significantly affected IPA Canonical Pathways for MSC exposed cells. This held true both when all of the significantly altered MSC genes were taken into account, and when only the genes unique to MSC were considered. The Biosynthesis of Steroids Pathway is a lipid metabolism pathway that controls the synthesis of cholesterol, which is an essential component of cell membranes and a precursor in the production of bile acids, steroid hormones, and vitamin D.
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