NF-κB p65 Antisense Oligonucleotides May Serve as a Novel Molecular Approach for the Treatment of Patients with Ulcerative Colitis

Background tion of nuclear factor-kappa B (NF-κB), which controls transcription of various proinflammatory cytokine genes, has been shown to play a critical role in the pathogenesis of ulcerative colitis (UC). The aim of this study was to investigate if NF-κB p65 antisense oligonucleotides may affect the expression of NF-κB p65 and cytokines in lamina propria mononuclear cells (LPMCs) from patients with UC. s which were isolated from intestinal mucosal biopsy specimens from patients with UC, were cultured with or without NF-κB p65 antisense oligonucleotides, missense oligonucleotides and dexamethasone. NF-κB p65 expression was determined by Western blot analysis. The expression of cytokine mRNA was studied by reverse transcription-polymerase chain reaction (RT-PCR). Cytokine levels were measured by enzyme-linked immunosorbent assay. s p65 antisense oligonucleotides resulted in downregulation of NF-κB p65 expression, blocked the expression of IL-1β mRNA and IL-8 mRNA, and strikingly reduced the production of IL-1β and IL-8. These effects were greater than those of dexamethasone in cultured LPMCs from patients with UC (p <0.05). sions ation of NF-κB p65 antisense oligonucleotides may serve as a novel molecular approach for the treatment of patients with UC.