Expression of MDR1 gene encoding P-glycoprotein is significantly increased in active pulmonary tuberculomas

Abstract

P-glycoprotein (P-gp) is a transporter which acts as an export pump and highly expressed in human lung cells. In various diseases, P-gp plays an important role both in regulating the activity of inflammation and in reducing the effectiveness of chemotherapy. The presence of pathogen, hypoxia and long-time treated enhances the MDR1 gene expression. All of these factors accompany TB process, but MDR1 expression and P-gp function in TB-inflammation is still unknown.

Aim and objectives: The aim of the study was to identify changes in the MDR1 gene expression at pulmonary TB patients with different activity of inflammation.

Methods: Material of tuberculomas was received from 56 patients and divided into 2 groups: with moderate and high activity of inflammation. Histological analysis, IHC-staining of M.tuberculosis, and confocal laser scanning microscopy were used for characteristic of tuberculomas. MDR1-expression was detected by real-time RT-PCR in different areas of tuberculomas: necrosis, perifocal zone and normal alveoli.

Results: The MDR1 highest values are detected only in the perifocal zones of high active tuberculomas, characterized by M. tuberculosis localization and immune cell infiltrates. In moderate tuberculomas, the level of MDR1 gene expression is 10 times lower than in active tuberculomas.

Conclusions: The relationship between the activity of TB inflammation and the level of the MDR1 gene expression was revealed. The highest expression level of the MDR1 gene was recorded in pulmonary TB with a high activity of specific inflammation. These data raise question about the cell population with the highest MDR1 gene expression values and its role in TB inflammation.