STABILIZED EXPRESSION OF MESSENGER-RNA IS ASSOCIATED WITH MYCOBACTERIAL RESISTANCE CONTROLLED BY NRAMP1

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, t he effect of the gene is pleiotropic and it has been suggested that th e gene controls macrophage priming for activation. We have found that the functional capacity of macrophages from Mycobacterium bovis BCG-su sceptible mice can be suppressed by corticosterone, while the function of macrophages from BCG-resistant mice remains unaffected. In this st udy, me 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 cortico sterone accelerates the decay of Nramp1 mRNA. The mRNA of IFN-gamma-in duced genes of macrophages from BCG-resistant mice was more stable tha n the mRNA of macrophages from BCS-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 macr ophage activation, thus accounting for the functional differences that have been attributed to these macrophage populations.