The anti-inflammatory and pro-resolution effects of aspirin-triggered RvD1 (AT-RvD1) on peripheral blood mononuclear cells from patients with severe asthma

Int Immunopharmacol. 2016 Jun:35:142-148. doi: 10.1016/j.intimp.2016.03.014. Epub 2016 Apr 16.

Abstract

Asthma is an inflammatory disease that is characterized by a predominance of eosinophils and/or neutrophils in the airways. In the resolution of inflammation, lipid mediators such as resolvin D1 (RvD1) and its epimer aspirin-triggered RvD1 (AT-RvD1) are produced and demonstrate anti-inflammatory and pro-resolution effects. In experimental models such as airway allergic inflammation induced by ovalbumin in mice, RvD1 and AT-RvD1 alleviate some of the most important phenotypes of asthma. Here, we demonstrated the effects of AT-RvD1 on peripheral blood mononuclear cells (PBMCs) from healthy individuals and patients with severe asthma stimulated with lipopolysaccharide (LPS) or Dermatophagoides pteronyssinus (DM). AT-RvD1 (100nM) reduced the concentration of TNF-α in PBMCs from healthy individuals and patients with severe asthma stimulated with LPS or DM. In addition, AT-RvD1 lowered the production of IL-10 only in PBMCs from patients with severe asthma stimulated with LPS. These effects were associated in part with decreasing NF-κB activation. Moreover, AT-RvD1 significantly increased phagocytosis of apoptotic neutrophils by monocytes from patients with severe asthma. In conclusion, AT-RvD1 demonstrated both anti-inflammatory and pro-resolution effects in PBMCs from patients with severe asthma and could become in the future an alternative treatment for asthma.

Keywords: AT-RvD1; Asthma; Dermatophagoides pteronyssinus; Lipopolysaccharide.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Aspirin / chemistry
  • Asthma / drug therapy*
  • Asthma / immunology
  • Cells, Cultured
  • Dermatophagoides pteronyssinus
  • Docosahexaenoic Acids / chemistry
  • Docosahexaenoic Acids / pharmacology*
  • Humans
  • Interleukin-10 / metabolism
  • Leukocytes, Mononuclear / drug effects*
  • Leukocytes, Mononuclear / immunology
  • Mice
  • Neutrophils / drug effects*
  • Neutrophils / physiology
  • Phagocytosis / drug effects
  • Signal Transduction / drug effects
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Anti-Inflammatory Agents
  • IL10 protein, human
  • Tumor Necrosis Factor-alpha
  • resolvin D1
  • Interleukin-10
  • Docosahexaenoic Acids
  • Aspirin