title: Stabilized expression of mRNA is associated with mycobacterial resistance controlled by Nramp1.
abstract: Control of innate resistance to the growth of mycobacteria is mediated by a gene termed Nramp1. Although the role of the protein product of Nramp1 in mediating resistance to mycobacterial growth is not known, the effect of the gene is pleiotropic and it has been suggested that the gene controls macrophage priming for activation. We have found that the functional capacity of macrophages from Mycobacterium bovis BCG-susceptible mice can be suppressed by corticosterone, while the function of macrophages from BCG-resistant mice remains unaffected. In this study, we show that corticosterone differentially affects the stability of mRNAs of several recombinant gamma interferon (rIFN-gamma)-induced genes. Treatment of macrophages from BCG-susceptible mice with corticosterone accelerates the decay of Nramp1 mRNA. The mRNA of IFN-gamma-induced genes of macrophages from BCG-resistant mice was more stable than the mRNA of macrophages from BCG-susceptible mice in the presence or absence of corticosterone. The results of this investigation suggest that Nramp1 acts by stabilizing the mRNA of genes associated with macrophage activation, thus accounting for the functional differences that have been attributed to these macrophage populations.
authors.affiliation: Department of Microbiology, The Ohio State University, Columbus 43210, USA.
authors.forename: D H
authors.initials: DH
authors.lastname: Brown
authors.forename: W P
authors.initials: WP
authors.lastname: Lafuse
authors.forename: B S
authors.initials: BS
authors.lastname: Zwilling
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000096:biosynthesis / Q000187:drug effects / Q000502:physiology*; D027682:Cation Transport Proteins; D003345:Corticosterone / Q000494:pharmacology; D004198:Disease Susceptibility; D005260:Female; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects / Q000276:immunology*; D007113:Immunity, Innate / Q000235:genetics; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007371:Interferon-gamma / Q000494:pharmacology; D008262:Macrophage Activation / Q000187:drug effects / Q000235:genetics; D008264:Macrophages / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D008565:Membrane Proteins / Q000096:biosynthesis / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009163:Mycobacterium bovis / Q000187:drug effects / Q000235:genetics* / Q000276:immunology*; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000187:drug effects; D014158:Transcription, Genetic / Q000187:drug effects; D000099173:Natural Resistance-associated Macrophage Protein 1
chemical_list: D002352:Carrier Proteins; D027682:Cation Transport Proteins; D003345:Corticosterone; D007166:Immunosuppressive Agents; D007371:Interferon-gamma; D008565:Membrane Proteins; D012333:RNA, Messenger; D000099173:Natural Resistance-associated Macrophage Protein 1