Fecal lipocalin 2, a sensitive and broadly dynamic non-invasive biomarker for intestinal inflammation.
Fecal lipocalin 2, a sensitive and broadly dynamic non-invasive biomarker for intestinal inflammation.
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DOI：
10.1371/journal.pone.0044328
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Vijay-Kumar M
中科院分区：
文献类型：
--
作者：
Chassaing B;Srinivasan G;Delgado MA;Young AN;Gewirtz AT;Vijay-Kumar M
炎症已被经典地定义为组织病理学，特别是通过免疫细胞浸润的存在。然而，最近的研究表明，“低度”炎症在从代谢综合征到癌症的各种疾病中起作用，这是由促炎基因表达的适度升高所定义的。因此，需要具有成本效益的非侵入性生物标志物，理想情况下，其具有检测低度炎症的灵敏度，并且具有足够宽的动态范围以反映典型的强烈肠道炎症。在此，我们报告，为了评估肠道炎症，粪便脂质运载蛋白2（LCN-2），通过ELISA测量，服务于此目的。具体而言，使用充分表征的DSS结肠炎小鼠模型，我们观察到极低浓度的DSS（0.25和0.5%）适度但显著诱导粪便Lcn-2和肠道促炎细胞因子（IL-1β、CXCL 1、TNFα）表达，并在较高浓度的DSS（1.0和4.0%）下显著升高。正如预期的那样，仔细的组织病理学分析在低DSS浓度下仅注意到适度的免疫浸润，在较高DSS浓度下注意到稳健的结肠炎。相应地，仅在给予1.0和4.0%DSS的小鼠中检测到中性粒细胞产物髓过氧化物酶（MPO）水平升高。此外，粪便Lcn-2标志着IL-10缺陷小鼠中自发性结肠炎发展的严重程度。与组织病理学、MPO和q-RT-PCR不同，粪便Lcn-2的测定仅需要粪便样品，允许随时间推移进行测量，并且可以早在DSS施用后1天检测炎症。因此，通过ELISA检测粪便Lcn-2可以作为一种非侵入性的、灵敏的、动态的、稳定的和成本有效的手段来监测小鼠肠道炎症。
Inflammation has classically been defined histopathologically, especially by the presence of immune cell infiltrates. However, more recent studies suggest a role for "low-grade" inflammation in a variety of disorders ranging from metabolic syndrome to cancer, which is defined by modest elevations in pro-inflammatory gene expression. Consequently, there is a need for cost-effective, non-invasive biomarkers that, ideally, would have the sensitivity to detect low-grade inflammation and have a dynamic range broad enough to reflect classic robust intestinal inflammation. Herein, we report that, for assessment of intestinal inflammation, fecal lipocalin 2 (Lcn-2), measured by ELISA, serves this purpose. Specifically, using a well-characterized mouse model of DSS colitis, we observed that fecal Lcn-2 and intestinal expression of pro-inflammatory cytokines (IL-1β, CXCL1, TNFα) are modestly but significantly induced by very low concentrations of DSS (0.25 and 0.5%), and become markedly elevated at higher concentrations of DSS (1.0 and 4.0%). As expected, careful histopathologic analysis noted only modest immune infiltrates at low DSS concentration and robust colitis at higher DSS concentrations. In accordance, increased levels of the neutrophil product myeloperoxidase (MPO) was only detected in mice given 1.0 and 4.0% DSS. In addition, fecal Lcn-2 marks the severity of spontaneous colitis development in IL-10 deficient mice. Unlike histopathology, MPO, and q-RT-PCR, the assay of fecal Lcn-2 requires only a stool sample, permits measurement over time, and can detect inflammation as early as 1 day following DSS administration. Thus, assay of fecal Lcn-2 by ELISA can function as a non-invasive, sensitive, dynamic, stable and cost-effective means to monitor intestinal inflammation in mice.
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DOI：
10.4049/jimmunol.1200892
发表时间：
2012-08-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Srinivasan G;Aitken JD;Zhang B;Carvalho FA;Chassaing B;Shashidharamurthy R;Borregaard N;Jones DP;Gewirtz AT;Vijay-Kumar M
通讯作者：
Vijay-Kumar M
影响因子：
4.4
作者：
Cowland, Jack B.;Muta, Tatsushi;Borregaard, Niels
通讯作者：
Borregaard, Niels
DOI：
10.1097/00042737-200208000-00002
发表时间：
2002-08-01
影响因子：
2.1
作者：
Aadland, E;Fagerhol, MK
通讯作者：
Fagerhol, MK
磷脂酰胆碱的肠道菌群代谢促进心血管疾病。
影响因子：
64.8
作者：
Wang, Zeneng;Klipfell, Elizabeth;Bennett, Brian J.;Koeth, Robert;Levison, Bruce S.;Dugar, Brandon;Feldstein, Ariel E.;Britt, Earl B.;Fu, Xiaoming;Chung, Yoon-Mi;Wu, Yuping;Schauer, Phil;Smith, Jonathan D.;Allayee, Hooman;Tang, W. H. Wilson;DiDonato, Joseph A.;Lusis, Aldons J.;Hazen, Stanley L.
通讯作者：
Hazen, Stanley L.
影响因子：
29.4
作者：
Castaneda, FE;Walia, B;Sitaraman, SV
通讯作者：
Sitaraman, SV