Correlations between expression levels of genes encoding multifunctional YB-1 protein, inflammatory cytokines and multidrug resistance P-gp protein in surgical material from patients with lung tuberculosis

Abstract

YB-1 is a multifunctional protein, being a transcription factor involved in the regulation of numerous cellular processes. YB-1 is an important factor in molecular cascades that regulate the response to the pathogen invasion, inflammatory activity, as well as efficient curation and healing. We suggest that YB-1 may also play an important role in pulmonary tuberculosis. However, the YBX1 transcriptional activity and the role of the YB-1 protein in pathogenesis of this disease have not yet been determined. The aim of our study was to identify the most significant correlations between expression rates of YB-1 gene with expression of some key cytokine genes involved in the regulation of tuberculous inflammation (IL-6, IL-10, IFNγ, TGF-β, TNFα, IL-1β), hypoxia factor-1 (HIF1a) gene, and P-gp protein gene ABCB1 in the patients with pulmonary tuberculosis. Gene expression was determined by quantitative PCR in the samples obtained at surgery from 35 patients. Correlation and cluster analysis were performed based on the PCR results. A positive correlation was found between the expression of YBX1, TGFB1, and ABCB1 genes. Correlation between the expression of YBX1 and ABCB1 genes were moderate, whereas ABCB1 gene expression exhibited a strong positive correlation with HIF1A and IL6 genes. The strongest correlation was found between YBX1 and TGFB1 gene expression (r = 0.62). There is no correlation found between YBX1 and the genes encoding other cytokines. TGFB1 showed a moderate correlation with TNF (r = 0.56). The relationship of YBX1 with TGFB1 was confirmed by cluster analysis, thus demonstrating a single cluster of YBX1, TGFB1, TNF. We assume that the YBX1, TGFB1, TNF gene cluster forms a regulatory system that plays an important role in development of tuberculous inflammation. Our work expands the knowledge on the molecular genetic features in tuberculoma, a clinical form of pulmonary tuberculosis. We suggest that the YB-1 protein can potentially have different functions: (1) being a participant in tuberculous inflammation via the cytokine expression; (2) modulating the P-gp activity and changing the pharmacokinetics of anti-tuberculosis drugs, thus requiring future studies.

Keywords

• tuberculosis
• yb-1
• p-gp
• cytokines
• inflammation
• pcr