Louvet B, Buisine M P, Desreumaux P, Tremaine W J, Aubert J P, Porchet N, Capron M, Cortot A, Colombel J F, Sandborn W J
Laboratoire de recherche sur les MICI (CRI 4U004B), Centre Hospitalier Universitaire (CHU), Lille, France.
Inflamm Bowel Dis. 1999 Aug;5(3):174-81. doi: 10.1097/00054725-199908000-00005.
Our goal was to determine the effect of transdermal nicotine on cytokine and mucin gene transcription in ulcerative colitis (UC). Sixty-four nonsmoking patients with active UC were randomly assigned to transdermal nicotine (maximum dose 22 mg/day) or placebo for 4 weeks. Clinical assessment and colonic mucosal biopsies were obtained at entry and after 4 weeks. Inflammatory and immunoregulatory cytokines were assessed by qualitative reverse transcriptase-polymerase chain reaction (RT-PCR). Based on this initial screen. IL-8 mRNA levels were measured by RT-competitive PCR. MUC1, MUC2, MUC3, MUC4, MUC5AC, MUC5B, and MUC6 mRNA concentrations were measured by quantitative dot blot analysis. Cytokine mRNA expression, except for IL-8, was similar in all patients. IL-8 mRNA levels were significantly decreased in the colonic mucosa of nicotine-treated patients who improved (p = 0.04). IL-8 mRNA values were similar before and after treatment in nonresponding nicotine-treated patients and in all placebo-treated patients. Mucin gene expression was similar in all patient groups. Beneficial effects of transdermal nicotine in active UC may result from decrease of IL-8 expression at the transcriptional level. Transdermal nicotine has no effect on mucin gene transcription.
我们的目标是确定经皮尼古丁对溃疡性结肠炎(UC)中细胞因子和黏蛋白基因转录的影响。64名患有活动性UC的非吸烟患者被随机分配接受经皮尼古丁(最大剂量22毫克/天)或安慰剂治疗4周。在入组时和4周后进行临床评估并获取结肠黏膜活检样本。通过定性逆转录聚合酶链反应(RT-PCR)评估炎性和免疫调节细胞因子。基于此初步筛选,通过RT竞争PCR测量白细胞介素-8(IL-8)mRNA水平。通过定量斑点印迹分析测量黏蛋白1(MUC1)、黏蛋白2(MUC2)、黏蛋白3(MUC3)、黏蛋白4(MUC4)、黏蛋白5AC(MUC5AC)、黏蛋白5B(MUC5B)和黏蛋白6(MUC6)mRNA浓度。除IL-8外,所有患者的细胞因子mRNA表达相似。在病情改善的尼古丁治疗患者的结肠黏膜中,IL-8 mRNA水平显著降低(p = 0.04)。在无反应的尼古丁治疗患者和所有安慰剂治疗患者中,治疗前后的IL-8 mRNA值相似。所有患者组中的黏蛋白基因表达相似。经皮尼古丁对活动性UC的有益作用可能源于转录水平上IL-8表达的降低。经皮尼古丁对黏蛋白基因转录无影响。