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

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 l...

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Published in:Clinical immunology (Orlando, Fla.) Fla.), 2018-05, Vol.190, p.74-83
Main Authors: Guimarães, Francielle Rodrigues, Sales-Campos, Helioswilton, Nardini, Viviani, da Costa, Thiago Alvares, Fonseca, Monique Thaís Costa, Júnior, Virmondes Rodrigues, Sorgi, Carlos Artério, da Silva, João Santana, Chica, Javier Emílio Lazo, Faccioli, Lúcia Helena, de Barros Cardoso, Cristina Ribeiro
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Language:English
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Summary: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 (LTB4) 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 LTB4, underline skin inflammation that follows skin injury and their neutralization may be an important strategy to improve cutaneous healing. •Inhibition of 5-lipoxygenase (5-LO) improved cutaneous wound healing and reduced inflammatory infiltrate in the skin.•Improved repair in the abscence of 5-LO was related to reduced TNF-α and better tissue remodeling.•Inhibition of cysteinyl leukotriene (cysLT) and LTB4 receptors confirmed the role of 5-LO products in cutaneous repair.•5-LO products underline skin inflammation and their neutralization may be an important strategy to improve skin healing.
ISSN:1521-6616
1521-7035
DOI:10.1016/j.clim.2017.08.022