Effects of Supplemental Calcium and Vitamin D on Expression of Toll-Like Receptors and Phospho-IKKα/β in the Normal Rectal Mucosa of Colorectal Adenoma Patients.
Effects of Supplemental Calcium and Vitamin D on Expression of Toll-Like Receptors and Phospho-IKKα/β in the Normal Rectal Mucosa of Colorectal Adenoma Patients.
复制标题
DOI：
10.1158/1940-6207.capr-18-0123
复制
发表时间：
2018-11
期刊：
影响因子：
--
通讯作者：
Fedirko V
中科院分区：
文献类型：
--
作者：
Hodge R;Mandle HB;Ray S;Tandon S;Peterson M;Henry A;Jahan FA;Bostick RM;Baron JA;Barry EL;Yacoub R;Rutherford RE;Seabrook ME;Fedirko V
结直肠中的慢性炎症是结直肠致癌的重要因素，它可以通过促炎信号通路的激活来触发，例如由Toll样受体（TLR）和核因子κB（NF-κB）启动的信号通路。B）。虽然实验证据支持钙和维生素D可能改变结肠直肠中的这些促炎途径，但这些方面的人体数据很少。我们研究了补充钙（每天1,200 mg）和/或维生素D3（每天1,000 IU）对来自结直肠腺瘤复发化学预防临床试验的105名参与者的炎症信号通路相关生物标志物的影响。我们使用标准化、自动化免疫组织化学和定量图像分析评估了正常直肠隐窝上皮和间质中分别识别细菌组分脂多糖和鞭毛蛋白的TLR 4和TLR 5以及炎症生物标志物磷酸化IKK α/β（pIKKα/β）的表达。治疗一年后，单独或联合补充维生素D或钙，直肠粘膜中的TLR 4、TLR 5和pIKKα/β表达没有统计学显著变化。一些基线参与者特征，包括体重指数、无蒂锯齿状腺瘤病史、高红肉/加工肉摄入量和高水平直肠上皮细胞增殖（通过MIB-1/Ki-67测量），与TLR或pIKKα/β的基线表达较高相关。我们的研究结果表明，维生素D和钙可能对所研究的生物标志物没有实质性影响。然而，几种可改变的生活方式因素可能与正常直肠粘膜中的TLR和pIKKα/β表达相关，支持其作为结直肠肿瘤的潜在可治疗的癌前风险因素的未来研究。
Chronic inflammation in the colorectum, a significant contributor to colorectal carcinogenesis, can be triggered by the activation of pro-inflammatory signaling pathways such as those initiated by Toll-like receptors (TLRs) and nuclear factor κB (NF-κB). Although experimental evidence supports calcium and vitamin D potentially modifying these pro-inflammatory pathways in the colorectum, human data in these regards are scarce. We investigated supplemental calcium (1,200 mg daily) and/or vitamin D3 (1,000 IU daily) effects on inflammatory signaling pathway-related biomarkers in a subset of 105 participants from a colorectal adenoma recurrence chemoprevention clinical trial. We assessed expression of TLR4 and TLR5, which recognize the bacterial components lipopolysaccharides and flagellin, respectively, and phospho-IKKα/β (pIKKα/β), a biomarker of inflammation, in the normal-appearing rectal crypt epithelium and stroma using standardized, automated immunohistochemistry and quantitative image analysis. Following one year of treatment, TLR4, TLR5, and pIKKα/β expression in the rectal mucosa did not statistically significantly change with vitamin D or calcium supplementation, taken alone or in combination. Several baseline participant characteristics, including body mass index, history of sessile serrated adenomas, high red/processed meat intake, and high levels of rectal epithelial cell proliferation (as measured by MIB-1/Ki-67), were associated with higher baseline expression of TLRs or pIKKα/β. Our findings suggest that vitamin D and calcium may have no substantial effect on the investigated biomarkers. However, several modifiable lifestyle factors may be associated with TLRs and pIKKα/β expression in the normal rectal mucosa, supporting their future investigation as potentially treatable, pre-neoplastic risk factors for colorectal neoplasms.