Circulating S100A8/A9 is potentially a biomarker that could reflect the severity of experimental colitis in rats
Circulating S100A8/A9 is potentially a biomarker that could reflect the severity of experimental colitis in rats
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DOI：
10.1016/j.heliyon.2020.e03470
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发表时间：
2020-02-01
期刊：
影响因子：
4
通讯作者：
Ikemoto, Masaki
中科院分区：
文献类型：
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作者：
Okada, Kohki;Itoh, Hiroshi;Ikemoto, Masaki
目的：循环S100A8/A9（钙保护蛋白）在溃疡性结肠炎（UC）患者中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。主要方法：采用实验动物（大鼠）验证血清S100A8/A9作为生物标志物的临床意义。以5%葡聚糖硫酸钠（DSS）单独（UCR）或5%葡聚糖硫酸钠加他克莫司（TMR）给药大鼠进行实验。采用酶联免疫吸附法（elisa）测定两组大鼠血清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。苏木精-伊红染色观察大鼠小肠组织损伤情况。统计分析这些炎症生物标志物的血清浓度与直肠组织组织学评分的关系。主要发现：通过elisa检测，UCR中r-S100A8/A9的血清浓度不仅与CRP，而且与一些炎性细胞因子的浓度几乎没有相关性。UCR明显观察到直肠组织，主要是大肠上皮结构的恶化，但没有TMR严重。UCR直肠组织的组织学评分与血清r-S100A8/A9水平显著相关，但与其他炎症生物标志物无关。巨噬细胞在脂多糖刺激下积极产生r-S100A8/A9，并在循环中快速分泌。因此，血清r-S100A8/A9水平随实验性UC的严重程度而变化。结论：循环r-S100A8/A9是一种有用的实验性UC生物标志物，其血清水平与疾病严重程度相关，可通过组织学评分判断。
Aims: 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.Main methods: 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.Principle findings: 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.Conclusion: 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.