Crucial involvement of the CX3CR1-CX3CL1 axis in dextran sulfate sodium-mediated acute colitis in mice
Crucial involvement of the CX3CR1-CX3CL1 axis in dextran sulfate sodium-mediated acute colitis in mice
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DOI：
10.1189/jlb.1109768
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发表时间：
2010-07-01
影响因子：
5.5
通讯作者：
Mukaida, Naofumi
中科院分区：
文献类型：
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作者：
Kostadinova, Feodora I.;Baba, Tomohisa;Mukaida, Naofumi
摄入DSS溶液可在啮齿动物中诱导急性结肠炎，伴有大量中性粒细胞和巨噬细胞浸润，与UC患者急性期观察到的病理变化相似。与此同时，DSS摄入增强了结肠中一种有效的巨噬细胞趋化因子CX 3CL 1/fractalkine及其受体CX 3CR 1的表达。WT而非CX 3CR 1缺陷小鼠在摄入DSS后表现出显著的体重减轻和结肠缩短。此外，与WT小鼠相比，CX 3CR 1缺陷小鼠中的炎性细胞浸润减弱，同时腺体结构的破坏减少。DSS摄入增强了WT小鼠中巨噬细胞和硝基酪氨酸生成的结肠内iNOS表达，但CX 3CR 1缺陷小鼠中iNOS表达和硝基酪氨酸生成减弱。对骨髓嵌合小鼠的分析显示，骨髓来源的而非非骨髓来源的CX 3CR 1表达细胞是iNOS的主要来源。这些观察结果表明，CX 3CL 1-CX 3CR 1轴可以调节iNOS的表达，iNOS是DSS诱导的结肠炎的关键介质。因此，靶向CX 3CL 1-CX 3CR 1轴可有效治疗IBD如UC。J. Leukoc. 88：133-143; 2010.
Ingestion of DSS solution can induce in rodents acute colitis with a massive infiltration of neutrophils and macropahges, mimicking pathological changes observed in the acute phase of UC patients. Concomitantly, DSS ingestion enhanced the expression of a potent macrophage-tropic chemokine, CX3CL1/fractalkine, and its receptor, CX3CR1, in the colon. WT but not CX3CR1-deficient mice exhibited marked body weight loss and shortening of the colon after DSS ingestion. Moreover, inflammatory cell infiltration was attenuated in CX3CR1-deficient mice together with reduced destruction of glandular architecture compared with WT mice. DSS ingestion enhanced intracolonic iNOS expression by macrophages and nitrotyrosine generation in WT mice, but iNOS expression and nitrotyrosine generation were attenuated in CX3CR1-deficient mice. The analysis on bone marrow chimeric mice revealed that bone marrow-derived but not non-bone marrow-derived CX3CR1-expressing cells were a major source of iNOS. These observations would indicate that the CX3CL1-CX3CR1 axis can regulate the expression of iNOS, a crucial mediator of DSS-induced colitis. Thus, targeting the CX3CL1-CX3CR1 axis may be effective for the treatment of IBDs such as UC. J. Leukoc. Biol. 88: 133-143; 2010.