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The trichothecene deoxynivalenol (DON), a common contaminant of cereal-based foods, is a ribotoxic mycotoxin known to activate innate immune cells in vivo and in vitro. Although it is recognized that DON induces transcription and mRNA stabilization of inflammation-associated mRNAs in mononuclear phagocytes, it is not known if this toxin affects translation of selected mRNA species in the cellular pool. To address this question, we employed a focused inflammation/autoimmunity PCR array to compare DON-induced changes in profiles of polysome-associated mRNA transcripts (translatome) to total cellular mRNA transcripts (transcriptome) in the RAW 264.7 murine macrophage model. Exposure to DON at 250 ng/ml (0.84 µM) for 6 h induced robust expression changes in inflammatory response genes including cytokines, cytokine receptors, chemokines, chemokine receptors, and transcription factors, with 73% of the changes being highly comparable within transcriptome and translatome populations. When expression changes of selected representative inflammatory response genes in the polysome and cellular mRNA pools were quantified in a follow-up study by real-time PCR, closely coordinated regulation of the translatome and transcriptome was confirmed; however, modest but significant differences in the relative expression of some genes within the two pools were also detectable. Taken together, DON's capacity to alter translation expression of inflammation-associated genes appears to be driven predominantly by selective transcription and mRNA stabilization that have been reported previously; however, a small subset of these genes appear to be further regulated at the translational level.

Modulation of Inflammatory Gene Expression by the Ribotoxin Deoxynivalenol Involves Coordinate Regulation of the Transcriptome and Translatome