The inhibition of 5-Lipoxygenase (5-LO) products leukotriene B4 (LTB4) and cysteinyl leukotrienes (cysLTs) modulates the inflammatory response and improves cutaneous wound healing

The inhibition of 5-Lipoxygenase (5-LO) products leukotriene B4 (LTB4) and cysteinyl leukotrienes (cysLTs) modulates the inflammatory response and improves cutaneous wound healing
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DOI:
10.1016/j.clim.2017.08.022
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发表时间:
2018-05-01
影响因子:
8.6
通讯作者:
de Barros Cardoso, Cristina Ribeiro
de Barros Cardoso, Cristina Ribeiro
中科院分区:
医学3区
文献类型:
--
作者:
Guimaraes, Francielle Rodrigues;Sales-Campos, Helioswilton;de Barros Cardoso, Cristina Ribeiro

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为了分析酶5-脂氧合酶(5-LO)在皮肤修复中的参与,将WT伤口与5-LO缺陷小鼠(5-LO-/-)中的伤口进行比较,其呈现更快的闭合和减少的皮肤中的炎性浸润,以及引流淋巴结中增加的CD 4调节性T细胞标志物。5-LO-/-伤口也减少了TNF-α,CCL 11,CCL 7,CCL 2,CXCL 9,CCR 1和CXCR 2 mRNA表达的病变,除了差异细胞外基质重塑。此外,当在WT小鼠中拮抗半胱氨酰白三烯(cysLT)和白三烯(LTB 4)受体时,TNF-α表达显著降低,皮肤愈合更快,与5-LO-/-动物中的发现相似。最后,我们的研究结果表明,5-LO产品,在特殊的cysLT和LTB 4,强调皮肤损伤后的皮肤炎症和它们的中和可能是一个重要的策略,以改善皮肤愈合。(C)2017爱思唯尔公司All rights reserved.
To analyze the participation of the enzyme 5-lipoxygenase (5-LO) in skin repair, WT wounds were compared to those in 5-LO deficient mice (5-LO-/-), which presented faster closure and reduced inflammatory infiltrate in the skin, together with increased CD4 regulatory T cells markers in the draining lymph nodes. The 5-LO-/- wounds also had diminished TNF-alpha, CCL11, CCL7, CCL2, CXCL9, CCRI and CXCR2 mRNA expression in the lesions, besides differential extracellular matrix remodeling. Furthermore, when cysteinyl leukotriene (cysLT) and leukotriene (LTB4) receptors were antagonized in WT mice, there was a remarkable reduction in TNF-alpha expression and faster skin healing, similarly to the findings in 5-LO-/- animals. Finally, our results suggested that 5-LO products, in special cysLT and LTB4, underline skin inflammation that follows skin injury and their neutralization may be an important strategy to improve cutaneous healing. (C) 2017 Elsevier Inc. All rights reserved.