title: Modulation of inflammatory gene expression by the ribotoxin deoxynivalenol involves coordinate regulation of the transcriptome and translatome.
abstract: 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.
authors.affiliation: Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, Michigan 48824, USA.
authors.forename: Kaiyu
authors.initials: K
authors.lastname: He
authors.forename: Xiao
authors.initials: X
authors.lastname: Pan
authors.forename: Hui-Ren
authors.initials: HR
authors.lastname: Zhou
authors.forename: James J
authors.initials: JJ
authors.lastname: Pestka
mesh_terms: D000818:Animals; D018929:Cell Culture Techniques; D002460:Cell Line; D016207:Cytokines / Q000235:genetics*; D015536:Down-Regulation; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D051379:Mice; D014176:Protein Biosynthesis / Q000187:drug effects* / Q000276:immunology; D012333:RNA, Messenger / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D059467:Transcriptome / Q000187:drug effects* / Q000276:immunology; D014255:Trichothecenes / Q000633:toxicity*; D015854:Up-Regulation
chemical_list: D016207:Cytokines; D012333:RNA, Messenger; D014255:Trichothecenes; C007262:deoxynivalenol