Departments of Microbiology and Medical Microbiology and Immunology, The Ohio State University, Columbus, Ohio 43210 USA
Host resistance to the growth of
Mycobacterium avium and
Mycobacterium tuberculosis is controlled by a gene, termed
Nramp1, that maps
to chromosome 1 in mice. Activation of the HPA axis or treatment
of macrophages from susceptible mice with corticosterone suppresses
the expression of
Nramp1 mRNA and results in an increased susceptibility
to mycobacterial growth. In contrast, neither activation of
the HPA axis nor treatment of macrophages from resistant mice
with corticosterone results in an alteration in their resistance
or suppression of
Nramp1 expression. Investigation into the
mechanism of the differential response of the macrophages to
corticosterone indicated that differences were associated with
the stability of the mRNA in macrophages from BCG-resistant
mice. Thus, corticosterone induced the accelerated degradation
of
Nramp1 mRNA as well as mRNA of several other macrophage activation
genes in macrophages from BCG-susceptible mice. Treatment of
macrophages with corticosterone before the induction of
Nramp1 resulted in the accelerated degradation of mRNA in macrophages
from both resistant and susceptible mice. The
Nramp1 gene product
appears to protect the mRNA of macrophage activation genes from
degradation induced by corticosterone by an iron-dependent mechanism.
