Okada Kohki, Itoh Hiroshi, Ikemoto Masaki
Department of Medical Technology and Sciences, Faculty of Health Sciences, Kyoto Tachibana University, Kyoto, 607-8175, Japan.
Faculty of Bioscience, Nagahama Institute of Bio-Science and Technology, Shiga, 526-0829, Japan.
Heliyon. 2020 Feb 29;6(2):e03470. doi: 10.1016/j.heliyon.2020.e03470. eCollection 2020 Feb.
The clinical significance of circulating S100A8/A9 (calprotectin) in patients with ulcerative colitis (UC) is poorly understood. We examined whether serum S100A8/A9 is a good biomarker for UC, and whether the serum level is a useful index for the severity of the disease.
Experimental animal (rats) were used to verify clinical significance of serum S100A8/A9 as a biomarker. Rats treated with 5% dextran sulfate sodium (DSS) alone (UCR) or with 5%DSS plus tacrolimus (TMR) were subjected to the experiment. The serum concentrations of rat S100A8/A9 (r-S100A8/A9) and other inflammatory biomarkers, such as C-reactive protein (CRP) and inflammatory cytokines, in the both groups were measured using enzyme-linked immunosorbent assays (ELISAs). The tissue damage in the large intestinal tract was visualized by hematoxylin-eosin staining. The relationship between the serum concetrations of these inflammatory biomarkers and the histological scores of the rectal tissue was statistically analyzed.
As determined by the ELISAs, the serum concentration of r-S100A8/A9 in the UCR hardly correlated with those of not only CRP but also some inflammatory cytokines. The deterioration of the rectal tissue, mainly epithelium structure of a large intestine, in the UCR was clearly observed, but was not so severe as that in the TMR. The histological scores of the rectal tissue in the UCR significantly correlated with the serum level of r-S100A8/A9, but not with other inflammatory biomarkers. Furthermore, macrophages actively produced r-S100A8/A9 in response to stimulation with lipopolysaccharide and quickly secreted it in circulation. Therefore, the serum level of r-S100A8/A9 suggestively changes in accordance with the severity of experimental UC.
Circulating r-S100A8/A9 is a useful biomarker for experimental UC, and its serum level correlates with the disease severity as judged by histological score.
溃疡性结肠炎（UC）患者循环中S100A8/A9（钙卫蛋白）的临床意义尚不清楚。我们研究了血清S100A8/A9是否是UC的良好生物标志物，以及血清水平是否是疾病严重程度的有用指标。
使用实验动物（大鼠）验证血清S100A8/A9作为生物标志物的临床意义。单独用5%硫酸葡聚糖钠（DSS）处理的大鼠（UCR组）或用5%DSS加他克莫司处理的大鼠（TMR组）进行实验。使用酶联免疫吸附测定（ELISA）测量两组大鼠血清中S100A8/A9（r-S100A8/A9）和其他炎症生物标志物，如C反应蛋白（CRP）和炎症细胞因子的浓度。通过苏木精-伊红染色观察大肠组织损伤情况。对这些炎症生物标志物的血清浓度与直肠组织的组织学评分之间的关系进行统计学分析。
通过ELISA测定，UCR组大鼠血清中r-S100A8/A9的浓度不仅与CRP，而且与一些炎症细胞因子的浓度几乎没有相关性。在UCR组中明显观察到直肠组织的恶化，主要是大肠上皮结构的恶化，但不如TMR组严重。UCR组直肠组织的组织学评分与r-S100A8/A9的血清水平显著相关，但与其他炎症生物标志物无关。此外，巨噬细胞在受到脂多糖刺激时会积极产生r-S100A8/A9，并迅速将其分泌到循环中。因此，r-S100A8/A9的血清水平根据实验性UC的严重程度有提示性变化。
循环中的r-S100A8/A9是实验性UC的有用生物标志物，其血清水平与组织学评分判断的疾病严重程度相关。
