[The effects of nuclear factor-kappa B p65 antisense oligonucleotides on expression of proinflammatory cytokines in lamina propria mononuclear cells from patients with ulcerative colitis].
To investigate if nuclear factor-kappa B (NF-kappa B) p65 antisense oligonucleotides might affect the expression of NF-kappa B p65 and cytokines in lamina propria mononuclear cells(LPMC) from patients with ulcerative colitis (UC). LPMC were isolated from intestinal mucosal biopsy specimens from 3 patients with UC, and cultured with or without NF-kappa B p65 antisense oligonucleotides (5'-GGAACAGTTCGTCCTATGG-3'), missense oligonucleotides (5'-GGAACAGTTCGTCTATGG-3') and dexamethasone. NF-kappa B p65 expression was determined by western blot analysis. The expression of cytokine mRNA was studied by reversal transcription-polymerase chain reaction (RT-PCR). The cytokine levels were measured by enzyme linked immunosorbent assay. The results showed that NF-kappa B p65 antisense oligonucleotides resulted in down-regulation of NF-kappa B p65 expression, blocked the expression of IL-1 beta mRNA and IL-8 mRNA, and strikingly reduced the production of IL-1 beta and IL-8, and these effects were greater than those of dexamethasone in cultured LPMC from patients with UC(P < 0.05). Therefore, the application of NF-kappa B p65 antisense oligonucleotides may serve as a novel molecular approach for the treatment of patients with UC.
Gan
Huatian
H
Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu 610041.
Ouyang
Qin
Q
Chen
Youqin
Y
Liang
Feng
F
D002478:Cells, Cultured; D003093:Colitis, Ulcerative / Q000188:drug therapy / Q000473:pathology*; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D007375:Interleukin-1 / Q000096:biosynthesis / Q000235:genetics; D016209:Interleukin-8 / Q000096:biosynthesis / Q000235:genetics; D007413:Intestinal Mucosa / Q000166:cytology; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism; D016328:NF-kappa B / Q000096:biosynthesis* / Q000235:genetics; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis
D016207:Cytokines; D007375:Interleukin-1; D016209:Interleukin-8; D016328:NF-kappa B; D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger