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

BackgroundActivation 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.MethodsLPMCs, 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.ResultsNF-κB 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).ConclusionsApplication of NF-κB p65 antisense oligonucleotides may serve as a novel molecular approach for the treatment of patients with UC.