NF-kappaB p65 antisense oligonucleotides may serve as a novel molecular approach for the treatment of patients with ulcerative colitis.
BACKGROUND
Activation of nuclear factor-kappa B (NF-kappaB), 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-kappaB p65 antisense oligonucleotides may affect the expression of NF-kappaB p65 and cytokines in lamina propria mononuclear cells (LPMCs) from patients with UC.


METHODS
LPMCs, which were isolated from intestinal mucosal biopsy specimens from patients with UC, were cultured with or without NF-kappaB p65 antisense oligonucleotides, missense oligonucleotides and dexamethasone. NF-kappaB 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.


RESULTS
NF-kappaB p65 antisense oligonucleotides resulted in downregulation of NF-kappaB p65 expression, blocked the expression of IL-1beta mRNA and IL-8 mRNA, and strikingly reduced the production of IL-1beta and IL-8. These effects were greater than those of dexamethasone in cultured LPMCs from patients with UC (p <0.05).


CONCLUSIONS
Application of NF-kappaB p65 antisense oligonucleotides may serve as a novel molecular approach for the treatment of patients with UC.
Li
Zhi
Z
Department of Gastroenterology and Geriatric Medicine West China Hospital, Sichuan University, Chengdu, China.
Zhang
De Kui
DK
Yi
Wen Quan
WQ
Ouyang
Qin
Q
Chen
You Qin
YQ
Gan
Hua Tian
HT
D000328:Adult; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D003093:Colitis, Ulcerative / Q000378:metabolism / Q000628:therapy; D003907:Dexamethasone / Q000627:therapeutic use; D005260:Female; D006801:Humans; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009092:Mucous Membrane / Q000166:cytology / Q000473:pathology; D016376:Oligonucleotides, Antisense / Q000235:genetics / Q000378:metabolism* / Q000627:therapeutic use*; D051996:Transcription Factor RelA / Q000235:genetics / Q000378:metabolism* / Q000627:therapeutic use*
D000893:Anti-Inflammatory Agents; D053583:Interleukin-1beta; D016209:Interleukin-8; D016376:Oligonucleotides, Antisense; D051996:Transcription Factor RelA; D003907:Dexamethasone