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

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 (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.

Keywords: Cysteinyl leukotrienes; Inflammation; Leukotriene B4; Lipid mediators; Repair; Skin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arachidonate 5-Lipoxygenase / genetics
  • Arachidonate 5-Lipoxygenase / immunology*
  • Arachidonate 5-Lipoxygenase / metabolism
  • Cysteine / immunology*
  • Cysteine / metabolism
  • Cytokines / genetics
  • Cytokines / immunology*
  • Cytokines / metabolism
  • Female
  • Gene Expression / immunology
  • Inflammation Mediators / immunology*
  • Inflammation Mediators / metabolism
  • Leukotriene B4 / immunology*
  • Leukotriene B4 / metabolism
  • Leukotrienes / immunology*
  • Leukotrienes / metabolism
  • Mice, 129 Strain
  • Mice, Knockout
  • Skin / immunology
  • Skin / metabolism
  • Skin / pathology
  • Wound Healing / genetics
  • Wound Healing / immunology*

Substances

  • Cytokines
  • Inflammation Mediators
  • Leukotrienes
  • cysteinyl-leukotriene
  • Leukotriene B4
  • Arachidonate 5-Lipoxygenase
  • Cysteine