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Expression of inflammatory genes in the colon of ulcerative colitis patients varies with activity both at the mRNA and protein level

机译:溃疡性结肠炎患者结肠中炎症基因的表达随mRNA和蛋白质水平的活性而变化

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Background: Ulcerative colitis (UC) is a chronic inflammatory disorder of the gastrointestinal tract involving aberrant activation of innate and adaptive immune responses. We aimed to study the expression profiles of the susceptibility gene Nod1 and selected pro-and anti-inflammatory cytokines during different stages of UC. Methods: 65 patients with mild, severe or remission stage of UC, and 22 normal colon mucosal biopsies from control individuals were included in the study for measuring the expression of nucleotide binding oligomerization 1(Nod1) and related pro-and anti-inflammatory cytokines using quantitative reverse transcription-PCR (qRT-PCR).mRNA expression levels were then correlated with severity of disease. In order to check their expression at the protein level, immunohistochemistry (IHC) was performed using Nod1, TNF-α, IFN-γ, IL-17, IL-23 and IL-13 antibodies. Results: Significant increases in Nod1 expression with simultaneous increases in pro-inflammatory cytokines TNF-α, INF-γ, IL-17 and IL-23 mRNA levels were observed in patients with mild and severe ulcerative colitis versus control individuals. The expression levels reverted back towards normal levels in patients during remission.However,mRNA expression of selected anti-inflammatory cytokines such as IL-11 and IL-13 were substantially lower in patients compared with control samples when measured using qRT PCR. Levels of IL-10 however, although exhibiting a decreasing trend, did not attain significance. Conclusions: Our results show that with simultaneous increase in Nod1 expression, expression profiling of downstream inflammatory cytokines that are activated in UC patients, displayed different patterns according to the severity of the disease. These may be potential prognostic biomarkers for diagnosing UC patients.
机译:背景:溃疡性结肠炎(UC)是胃肠道的一种慢性炎症性疾病,涉及先天性和适应性免疫反应的异常激活。我们旨在研究易感性基因Nod1的表达谱以及在UC的不同阶段中选择的促炎和抗炎细胞因子。方法:本研究包括65例轻度,重度或缓解期UC患者,以及22例正常人的正常结肠粘膜活检组织,以使用该方法检测核苷酸结合寡聚化1(Nod1)以及相关促炎和抗炎细胞因子的表达。定量逆转录PCR(qRT-PCR)。然后将mRNA表达水平与疾病的严重程度相关。为了检查它们在蛋白质水平上的表达,使用Nod1,TNF-α,IFN-γ,IL-17,IL-23和IL-13抗体进行了免疫组织化学(IHC)。结果:在轻度和重度溃疡性结肠炎患者中,与对照组相比,Nod1表达显着增加,同时促炎性细胞因子TNF-α,INF-γ,IL-17和IL-23 mRNA水平同时升高。在缓解期间,患者的表达水平恢复到正常水平。但是,当使用qRT PCR测量时,与对照样品相比,患者中所选抗炎细胞因子(如IL-11和IL-13)的mRNA表达明显降低。然而,IL-10的水平虽然表现出下降的趋势,但是没有达到显着水平。结论:我们的结果表明,随着Nod1表达的同时增加,UC患者中激活的下游炎症细胞因子的表达谱根据疾病的严重程度呈现出不同的模式。这些可能是诊断UC患者的潜在预后生物标志物。

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