[Activation of nuclear factor-kappaB and its relationship with cytokine gene expression in colonic mucosa of ulcerative colitis patients]

Abstract

Objective: To investigate the activation of nuclear factor-kappaB (NF-kappaB) and its relationship with expression of cytokine mRNA in intestinal mucosal biopsy specimens from patients with ulcerative colitis (UC).

Methods: 31 cases with UC were included in the study. 17 cases received sulfasalazine (SASP) or SASP and glucocorticoid treatment. 14 cases did not receive any medication related with UC. Normal mucosa from 11 colon cancer cases served as control. Ten pieces of intestinal mucosal biopsy specimens were obtained from each patient. NF-kappaB DNA binding activity was evaluated with electrophoretic mobility shift assay (EMSA). Expression of cytokine mRNA were studied with reversal tanscription-polymerase chain reaction (RT-PCR).

Results: (1) The expression of IL-1beta mRNA and IL-8 mRNA was increased significantly in patients with UC, as compared with that in the control specimens (P < 0.05) and had a significant positive correlation with NF-kappaB DNA binding activity (r = 0.8363, P < 0.05; r = 0.6024, P < 0.05, respectively). (2) Glucocorticoids and SASP strongly inhibited NF-kappaB activation and signficantly decreased the expression of IL-1beta mRNA and IL-8 mRNA.

Conclusions: NF-kappaB is a major and essential factor in regulating the expression of cytokine and plays a fundamental role in the pathogenesis of UC. SASP and glucocorticoids decrease cytokine expression via inhibition of NF-kappaB activation.