Mohammadi Mojgan, Zahedi Mohammad Javad, Nikpoor Amin Reza, Baneshi Mohammad Reza, Hayatbakhsh Mohammad Mahdi
Physiology Research Centre, Kerman University of Medical Sciences, Kerman, Iran, e-mail:
Iran J Immunol. 2013 Jun;10(2):83-92.
Inflammatory bowel disease, an autoimmune disease, has two clinical manifestations including Crohn's disease and ulcerative colitis (UC). IL-17 has been the target of intensive research in autoimmune diseases. The influence of Toll like receptor 4 (TLR-4) gene polymorphisms on IL-17 production has also been revealed in UC patients and tissue inflammation in mice.
To investigate the association between the TLR-4 gene polymorphisms, Asp299Gly and Thr399Ile and IL-17 serum levels with ulcerative colitis. Additionally, we aimed to study modulation effects of forenamed gene polymorphisms on IL-17 serum levels in UC patients and controls.
A total of 256 healthy controls and 85 UC patients enrolled in our study. DNA was extracted and PCR-RFLP technique was employed to determine Asp299Gly and Thr399Ile polymorphisms in TLR-4 gene and IL-17 serum levels were measured by ELISA method.
There was no significant difference between the frequency of Asp299Gly A>G and Thr399Ile C>T in UC patients and controls. While IL-17 serum levels in UC patients were significantly higher than controls (p=0.003), no significant difference in IL-17 levels between different genotypes existed. Additionally, a significant inverse relationship was observed between hemoglobin level and IL-17 serum levels in UC patients (p=0.039).
Increased IL-17 serum levels in our UC patients might be explained through the synergistic activity of IL-17/IL-23 axis and pro-inflammatory cytokines, causing severe clinical outcome in patients with IBD. The prolonged excretion of blood in stool driven by inflammatory process which causes iron metabolism disorder and anemia may elucidate the inverse correlation between hemoglobin and IL-17 serum levels in UC patients. Lack of association between the TLR-4 gene polymorphisms and UC in our study was consistent with the results from other Caucasian populations.
炎症性肠病是一种自身免疫性疾病，有两种临床表现，即克罗恩病和溃疡性结肠炎（UC）。白细胞介素-17（IL-17）一直是自身免疫性疾病深入研究的靶点。Toll样受体4（TLR-4）基因多态性对IL-17产生的影响也已在UC患者及小鼠组织炎症中得到揭示。
探讨TLR-4基因多态性（Asp299Gly和Thr399Ile）与溃疡性结肠炎患者IL-17血清水平之间的关联。此外，我们旨在研究上述基因多态性对UC患者及对照者IL-17血清水平的调节作用。
共有256名健康对照者和85名UC患者纳入我们的研究。提取DNA，并采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）技术测定TLR-4基因中的Asp299Gly和Thr399Ile多态性，采用酶联免疫吸附测定（ELISA）法检测IL-17血清水平。
UC患者和对照者中Asp299Gly A>G及Thr399Ile C>T的频率无显著差异。虽然UC患者的IL-17血清水平显著高于对照者（p=0.003），但不同基因型之间的IL-17水平无显著差异。此外，在UC患者中观察到血红蛋白水平与IL-17血清水平之间存在显著负相关（p=0.039）。
我们的UC患者中IL-17血清水平升高可能通过IL-17/IL-23轴与促炎细胞因子的协同活性来解释，这导致炎症性肠病患者出现严重的临床结局。炎症过程导致的粪便中长期失血，进而引起铁代谢紊乱和贫血，这可能解释了UC患者中血红蛋白与IL-17血清水平之间的负相关关系。我们的研究中TLR-4基因多态性与UC之间缺乏关联，这与其他白种人群的研究结果一致。
