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

• Published in: Clinical immunology (Orlando, Fla.) Vol. 190; pp. 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
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.05.2018
• Subjects: Animals; Arachidonate 5-Lipoxygenase - genetics; Arachidonate 5-Lipoxygenase - immunology; Arachidonate 5-Lipoxygenase - metabolism; Cysteine - immunology; Cysteine - metabolism; Cysteinyl leukotrienes; Cytokines - genetics; Cytokines - immunology; Cytokines - metabolism; Female; Gene Expression - immunology; Inflammation; Inflammation Mediators - immunology; Inflammation Mediators - metabolism; Leukotriene B4; Leukotriene B4 - immunology; Leukotriene B4 - metabolism; Leukotrienes - immunology; Leukotrienes - metabolism; Lipid mediators; Mice, 129 Strain; Mice, Knockout; Repair; Skin; Skin - immunology; Skin - metabolism; Skin - pathology; Wound Healing - genetics; Wound Healing - immunology; Cysteinyl leukotrienes; Inflammation; Skin; Leukotriene B4; Repair; Lipid mediators
• ISSN: 1521-6616; 1521-7035
• DOI: 10.1016/j.clim.2017.08.022

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.