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5-脂氧合酶(5-LO)产物白三烯 B4(LTB)和半胱氨酰白三烯(cysLTs)的抑制作用可调节炎症反应,促进皮肤伤口愈合。

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

机构信息

Instituto de Ciências Biológicas e Naturais, Universidade Federal do Triângulo Mineiro, Uberaba, Minas Gerais, Brazil; Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, São Paulo, Brazil.

Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, São Paulo, Brazil.

出版信息

Clin Immunol. 2018 May;190:74-83. doi: 10.1016/j.clim.2017.08.022. Epub 2017 Sep 28.

Abstract

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-α, CCL11, CCL7, CCL2, CXCL9, CCR1 and CXCR2 mRNA expression in the lesions, besides differential extracellular matrix remodeling. Furthermore, when cysteinyl leukotriene (cysLT) and leukotriene (LTB) receptors were antagonized in WT mice, there was a remarkable reduction in TNF-α 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 LTB, underline skin inflammation that follows skin injury and their neutralization may be an important strategy to improve cutaneous healing.

摘要

为分析酶 5-脂氧合酶(5-LO)在皮肤修复中的作用,将 WT 创面与 5-LO 缺陷型小鼠(5-LO)的创面进行比较,结果显示后者的创面闭合更快,皮肤炎症浸润减少,引流淋巴结中 CD4 调节性 T 细胞标志物增加。5-LO 创面皮损处 TNF-α、CCL11、CCL7、CCL2、CXCL9、CCR1 和 CXCR2mRNA 的表达也减少,细胞外基质重塑出现差异。此外,当 WT 小鼠的半胱氨酰白三烯(cysLT)和白三烯(LTB)受体被拮抗时,TNF-α 的表达显著减少,皮肤愈合更快,与 5-LO 动物的结果相似。最后,我们的研究结果表明,5-LO 产物,特别是 cysLT 和 LTB,在皮肤损伤后的炎症反应中起重要作用,其中和可能是改善皮肤愈合的重要策略。

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