Methotrexate modulates folate phenotype and inflammatory profile in EA.hy 926 cells.
Methotrexate modulates folate phenotype and inflammatory profile in EA.hy 926 cells.
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DOI：
10.1016/j.ejphar.2014.03.004
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发表时间：
2014-06-05
影响因子：
5
通讯作者：
Whitehead, Alexander S.
中科院分区：
文献类型：
--
作者：
Summers, Carolyn M.;Hammons, Andrea L.;Arora, Jasbir;Zhang, Suhong;Jochems, Jeanine;Blair, Ian A.;Whitehead, Alexander S.
在低叶酸条件下生长的 EA.hy 926 细胞采用“促动脉粥样硬化”形态和生化表型。将药理学相关剂量的抗叶酸药物甲氨蝶呤 (MTX) 应用于维持在正常 (Hi) 和低 (Lo) 叶酸培养基中的 EA.hy 926 细胞。在两种叶酸条件下，MTX 都会抑制细胞增殖，但不会显着影响代谢活性。 MTX 处理的 Hi 细胞中的叶酸衍生物被耗尽，相对于未处理的细胞，叶酸衍生物的比例发生了变化。使用微阵列的转录谱分析表明，MTX 处理以类似的方式修饰 Hi 和 Lo 细胞的转录组。许多炎症相关基因，尤其是编码 C3 和 IL-8 的基因上调，而许多参与细胞分裂的基因下调。 C3 和 IL-8 的结果通过定量 RT-PCR 和 ELISA 得到证实。 MTX 似乎可以改变 EA.hy 926 细胞的炎症潜力，因此其治疗特性可能至少在某些条件下伴随着诱导促进和/或维持共病病理的基因产物子集。
EA.hy 926 cells grown under low folate conditions adopt a “pro-atherosclerotic” morphology and biochemical phenotype. Pharmacologically relevant doses of the antifolate drug methotrexate (MTX) were applied to EA.hy 926 cells maintained in normal (Hi) and low (Lo) folate culture media. Under both folate conditions, MTX caused inhibition of cell proliferation without significantly compromising metabolic activity. MTX treated Hi cells were depleted of folate derivatives, which were present in altered proportions relative to untreated cells. Transcript profiling using microarrays indicated that MTX treatment modified the transciptome in similar ways for both Hi and Lo cells. Many inflammation-related genes, most prominently those encoding C3 and IL-8, were up-regulated, whereas many genes involved in cell division were down-regulated. The results for C3 and IL-8 were confirmed by quantitative RT-PCR and ELISA. MTX appears to modify the inflammatory potential of EA.hy 926 cells such that its therapeutic properties may, at least under some conditions, be accompanied by the induction of a subset of gene products that promote and/or maintain comorbid pathologies.
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影响因子：
8.6
作者：
Hammons, Andrea L.;Summers, Carolyn M.;Whitehead, Alexander S.
通讯作者：
Whitehead, Alexander S.
影响因子：
5.3
作者：
Lu, Zhi-Yong;Jensen, Liselotte E.;Huang, Yuehua;Kealey, Carmel;Blair, Ian A.;Whitehead, Alexander S.
通讯作者：
Whitehead, Alexander S.
影响因子：
--
作者：
WILLIAMS, HJ;WILLKENS, RF;WARD, JR
通讯作者：
WARD, JR
影响因子：
2.8
作者：
Mitchell, Laura E.;Morales, Megan;Whitehead, Alexander S.
通讯作者：
Whitehead, Alexander S.
影响因子：
5.3
作者：
Brown, Karen S.;Huang, Yuehua;Whitehead, Alexander S.
通讯作者：
Whitehead, Alexander S.