Comparative expression of GC´s and GC´s converting enzymes in
the late phase of TB & T2D-TB lungs
Before evaluating the therapeutic effect of BEA, comparison among
non-infected control mice fed with chow diet, T2D, TB and T2D-TB groups
was done in the lungs of animals with late disease at day 120 of
infection as determined by immunohistochemistry, the presence of
corticosterone (active GC) and cortisone (inactive GC), as well as the
genetic expression of the GC converting enzymes determined by RT-PCR and
their cellular source by immunohistochemistry (Fig. 3). The lungs of
control non-infected mice showed occasional bronchial epithelial cells
with corticosterone positive immunostaining, while in T2D mice a clear
increase in the number and intensity of corticosterone was seen in
airways epithelium (Fig. 3 A). In the TB and T2D-TB groups the bronchial
epithelium was negative, and the pneumonic areas showed intense
corticosterone immunostaining in some lymphocytes and numerous
macrophages, being many of them vacuolated or foamy macrophages (Fig.
3A). In comparison with the control non-infected group, there was also a
significant increase in the genetic expression of 11-βHSD1 in T2D, TB
and T2D-TB groups, being macrophages from pneumonic areas the cells that
showed strong immunostaining to this enzyme (Fig. 3B). Thus, there is a
high expression of 11-βHSD1 and corticosterone production in the
inflammatory cells of pulmonary TB, which is even higher in mice with
T2D-TB.
Regarding inactive GC cortisone, the lungs from non-infected mice showed
positive immunostaining in the alveolar epithelium, which was lower in
T2D animals and quite strong in the TB lungs, while in T2D-TB was
slightly positive, almost negative (Fig. 3C). These immunohistochemical
results are well correlated with the 11-βHSD2 gene expression, which
showed significant higher expression in non-infected lungs, while it was
lower in TB, and the T2D-TB group showed the lowest (Fig. 3D).