Changes in expression of p53 and inflammatory factors in patients with ulcerative colitis.

Abstract

Ulcerative colitis (UC) is an important risk factor for the occurrence of colon cancer, and changes in expression of p53 and inflammatory factors are closely related to the pathogenesis of colon cancer. Therefore, changes in expression of p53 and inflammatory factors in UC were investigated to explore its intrinsic pathogenetic laws. The levels of inflammatory factors, such as interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), IL-10 and IL-4, in peripheral blood of UC patients and healthy adults were detected via enzyme-linked immunosorbent assay, and the changes in p53 expression were analyzed via immunohistochemistry and western blotting, and the correlation of p53 expression with changes in cytokines was also analyzed. Moreover, changes in 45S preribosomal ribonucleic acid (preRNA) transcriptional activity in four kinds of cell lines exposed to IL-6 were analyzed and determined by using reverse transcription-quantitative polymerase chain reaction. Finally, the C-myc protein expression after IL-6 stimulation was analyzed and evaluated via western blot analysis. The levels of IL-6 and TNF-α in peripheral blood in the UC patient group were significantly increased compared with those in the healthy adult group (P<0.01), while the levels of IL-10 and IL-4 in peripheral blood were significantly decreased compared with those in the healthy adult group (P<0.01). The p53 expression had a significant negative correlation with IL-6. The results showed that IL-6 activated C-myc messenger RNA (mRNA) translation, thereby upregulating the ribosomal RNA (rRNA) transcription. Additionally, IL-6 stimulated the mouse double minute 2 homolog (MDM2)-mediated proteasomal degradation of p53 by reducing the availability of ribosomal protein used for MDM2 binding, thus resulting in the downregulation of p53 protein expression. The findings of the study show that, expression level of IL-6 was increased in UC patients, which regulates the downregulation of p53 expression level and plays a role in tumorigenesis through enhancing cell proliferation and inhibiting apoptosis.