Figueroa-Gispert María Del Mar, Ramos-Lugo Claudia M, Ocasio-Malavé Carlimar, Scott Rizaldy P, Ahrendsen Jared T, Gomez-Samblas Mercedes, Osuna Antonio, Dorta-Estremera Stephanie M, Espino Ana M
Department of Microbiology and Medical Zoology, University of Puerto Rico-Medical Sciences Campus, San Juan, PR 00936, USA.
Mouse Histology & Phenotyping Laboratory, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
Cells. 2025 May 29;14(11):799. doi: 10.3390/cells14110799.
Ulcerative colitis (UC) is the most prevalent inflammatory bowel disease (IBD) in the USA. Current treatments present clinical limitations, underscoring the need for innovative therapeutics that promote an anti-inflammatory immune response. This study evaluates the anti-inflammatory potential of Fh15, a recombinant fatty acid binding protein, in a DSS-induced UC mouse model. Our results demonstrated that Fh15 treatment significantly ameliorated the severity of colitis by reducing the disease activity index (DAI) and histopathological scores. Moreover, Fh15 also decreased the serum levels of myeloperoxidase (MPO) and chitinase-3-like protein 1 (CHI3L1), and the expression of S100A9, a calcium and zinc binding protein, which is an important marker for the pathogenesis of UC. Furthermore, Fh15 downregulated pro-inflammatory cytokines TNFα and IL-1β in the distal colon, suggesting modulation of macrophage activity. Immunohistochemistry analysis revealed significantly reduced neutrophil and macrophage infiltration in UC Fh15-treated mice. These findings highlight the therapeutic potential of Fh15 for UC, as it modulates inflammatory responses, reduces leukocyte infiltration, and preserves colon integrity.
溃疡性结肠炎(UC)是美国最常见的炎症性肠病(IBD)。目前的治疗方法存在临床局限性,这凸显了对促进抗炎免疫反应的创新疗法的需求。本研究在葡聚糖硫酸钠(DSS)诱导的UC小鼠模型中评估了重组脂肪酸结合蛋白Fh15的抗炎潜力。我们的结果表明,Fh15治疗通过降低疾病活动指数(DAI)和组织病理学评分,显著改善了结肠炎的严重程度。此外,Fh15还降低了血清髓过氧化物酶(MPO)和几丁质酶-3样蛋白1(CHI3L1)的水平,以及S100A9(一种钙和锌结合蛋白,是UC发病机制的重要标志物)的表达。此外,Fh15下调了远端结肠中促炎细胞因子TNFα和IL-1β的表达,提示其对巨噬细胞活性的调节作用。免疫组织化学分析显示,在接受Fh15治疗的UC小鼠中,中性粒细胞和巨噬细胞浸润显著减少。这些发现突出了Fh15对UC的治疗潜力,因为它能调节炎症反应、减少白细胞浸润并维持结肠完整性。