Effect of BEA on the expression of 11-βHSD1 and 11-βHSD2,
corticosterone and cortisone in the lungs and liver.
In the lung, treatment with BEA in TB and T2D-TB groups induced
significant lower expression of 11-βHSD1 after one and two months of
treatment when compared with the control group (Fig. 5). This effect was
even more evident in the liver of T2D-TB group, which also showed
complete disappearance of steatosis and hyperglycemia (Fig. 6D).
The effects of BEA on 11-βHSD1 gene expression in the infected lung were
in concordance with the corticosterone immunehistochemistry staining,
and its quantitative evaluation by digital pathology (Fig. 5A). BEA
significantly decreased active corticosterone in TB and TB/T2D mice,
being more pronounced in the TB group (Fig. 5C). In contrast, the
expression of 11-βHSD2 after one and two months of BEA treatment showed
a significant increase in the TB group, and cortisone was increased in
both groups (Fig. 5D, and 5E).
Thus, it seems that BEA is a regulator of the genetic expression of
these enzymes in the lung and liver, inducing lower expression of
11-βHSD1 and higher gene expression of 11-βHSD2. In consequence BEA
induced lower production of active corticosterone and higher production
of inactive cortisone, which could contribute to increase the expression
of the pro-inflammatory cytokines TNF-α and IFN-γ decreasing the
pulmonary bacillary loads. In the liver BEA improved lipid and glucose
metabolism and normalized liver histology and glucose blood
concentrations.
Thus, BEA improved the immune response and metabolism of the comorbidity
T2D/TB, suggesting that it could be a potential new immune therapeutic
agent with beneficial immune, endocrine and metabolic activities.